Skip Navigation
Skip to contents

Diabetes Metab J : Diabetes & Metabolism Journal

Search
OPEN ACCESS

Search

Page Path
HOME > Search
5 "Appetite"
Filter
Filter
Article category
Keywords
Publication year
Authors
Funded articles
Original Articles
Basic Research
Article image
Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition
Ho Gyun Lee, Il Hyeon Jung, Byong Seo Park, Hye Rim Yang, Kwang Kon Kim, Thai Hien Tu, Jung-Yong Yeh, Sewon Lee, Sunggu Yang, Byung Ju Lee, Jae Geun Kim, Il Seong Nam-Goong
Diabetes Metab J. 2023;47(6):784-795.   Published online August 23, 2023
DOI: https://doi.org/10.4093/dmj.2022.0261
  • 2,601 View
  • 180 Download
  • 2 Web of Science
  • 2 Crossref
AbstractAbstract PDFPubReader   ePub   
Background
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are currently used to treat patients with diabetes. Previous studies have demonstrated that treatment with SGLT-2 inhibitors is accompanied by altered metabolic phenotypes. However, it has not been investigated whether the hypothalamic circuit participates in the development of the compensatory metabolic phenotypes triggered by the treatment with SGLT-2 inhibitors.
Methods
Mice were fed a standard diet or high-fat diet and treated with dapagliflozin, an SGLT-2 inhibitor. Food intake and energy expenditure were observed using indirect calorimetry system. The activity of hypothalamic neurons in response to dapagliflozin treatment was evaluated by immunohistochemistry with c-Fos antibody. Quantitative real-time polymerase chain reaction was performed to determine gene expression patterns in the hypothalamus of dapagliflozin-treated mice.
Results
Dapagliflozin-treated mice displayed enhanced food intake and reduced energy expenditure. Altered neuronal activities were observed in multiple hypothalamic nuclei in association with appetite regulation. Additionally, we found elevated immunosignals of agouti-related peptide neurons in the paraventricular nucleus of the hypothalamus.
Conclusion
This study suggests the functional involvement of the hypothalamus in the development of the compensatory metabolic phenotypes induced by SGLT-2 inhibitor treatment.

Citations

Citations to this article as recorded by  
  • Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition (Diabetes Metab J 2023;47:784-95)
    Jae Hyun Bae
    Diabetes & Metabolism Journal.2024; 48(1): 157.     CrossRef
  • Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition (Diabetes Metab J 2023;47:784-95)
    Ho Gyun Lee, Il Hyeon Jung, Byong Seo Park, Hye Rim Yang, Kwang Kon Kim, Thai Hien Tu, Jung-Yong Yeh, Sewon Lee, Sunggu Yang, Byung Ju Lee, Jae Geun Kim, Il Seong Nam-Goong
    Diabetes & Metabolism Journal.2024; 48(1): 159.     CrossRef
Drug/Regimen
Glucagon-Like Peptide-1 Receptor Agonist Differentially Affects Brain Activation in Response to Visual Food Cues in Lean and Obese Individuals with Type 2 Diabetes Mellitus
Jae Hyun Bae, Hyung Jin Choi, Kang Ik Kevin Cho, Lee Kyung Kim, Jun Soo Kwon, Young Min Cho
Diabetes Metab J. 2020;44(2):248-259.   Published online November 4, 2019
DOI: https://doi.org/10.4093/dmj.2019.0018
  • 8,951 View
  • 251 Download
  • 9 Web of Science
  • 9 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   
Background

To investigate the effects of a glucagon-like peptide-1 receptor agonist on functional brain activation in lean and obese individuals with type 2 diabetes mellitus (T2DM) in response to visual food cues.

Methods

In a randomized, single-blinded, crossover study, 15 lean and 14 obese individuals with T2DM were administered lixisenatide or normal saline subcutaneously with a 1-week washout period. We evaluated brain activation in response to pictures of high-calorie food, low-calorie food, and nonfood using functional magnetic resonance imaging and measured appetite and caloric intake in participants who were given access to an ad libitum buffet.

Results

Obese individuals with T2DM showed significantly greater activation of the hypothalamus, pineal gland, parietal cortex (high-calorie food vs. low-calorie food, P<0.05), orbitofrontal cortex (high-calorie food vs. nonfood, P<0.05), and visual cortex (food vs. nonfood, P<0.05) than lean individuals with T2DM. Lixisenatide injection significantly reduced the functional activation of the fusiform gyrus and lateral ventricle in obese individuals with T2DM compared with that in lean individuals with T2DM (nonfood vs. high-calorie food, P<0.05). In addition, in individuals who decreased their caloric intake after lixisenatide injection, there were significant interaction effects between group and treatment in the posterior cingulate, medial frontal cortex (high-calorie food vs. low-calorie food, P<0.05), hypothalamus, orbitofrontal cortex, and temporal lobe (food vs. nonfood, P<0.05).

Conclusion

Brain responses to visual food cues were different in lean and obese individuals with T2DM. In addition, acute administration of lixisenatide differentially affected functional brain activation in these individuals, especially in those who decreased their caloric intake after lixisenatide injection.

Citations

Citations to this article as recorded by  
  • Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition (Diabetes Metab J 2023;47:784-95)
    Jae Hyun Bae
    Diabetes & Metabolism Journal.2024; 48(1): 157.     CrossRef
  • GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans
    Kyu Sik Kim, Joon Seok Park, Eunsang Hwang, Min Jung Park, Hwa Yun Shin, Young Hee Lee, Kyung Min Kim, Laurent Gautron, Elizabeth Godschall, Bryan Portillo, Kyle Grose, Sang-Ho Jung, So Lin Baek, Young Hyun Yun, Doyeon Lee, Eunseong Kim, Jason Ajwani, Seo
    Science.2024; 385(6707): 438.     CrossRef
  • Glucagon-like peptide 1 agonist and effects on reward behaviour: A systematic review
    Sebastian Badulescu, Aniqa Tabassum, Gia Han Le, Sabrina Wong, Lee Phan, Hartej Gill, Cristian-Daniel Llach, Roger S. McIntyre, Joshua Rosenblat, Rodrigo Mansur
    Physiology & Behavior.2024; 283: 114622.     CrossRef
  • Clinical Consequences of Delayed Gastric Emptying With GLP-1 Receptor Agonists and Tirzepatide
    Ryan J Jalleh, Mark P Plummer, Chinmay S Marathe, Mahesh M Umapathysivam, Daniel R Quast, Christopher K Rayner, Karen L Jones, Tongzhi Wu, Michael Horowitz, Michael A Nauck
    The Journal of Clinical Endocrinology & Metabolism.2024;[Epub]     CrossRef
  • Diabetes remission and relapse following an intensive metabolic intervention combining insulin glargine/lixisenatide, metformin and lifestyle approaches: Results of a randomised controlled trial
    Natalia McInnes, Stephanie Hall, Heather A. Lochnan, Stewart B. Harris, Zubin Punthakee, Ronald J. Sigal, Irene Hramiak, Mohammed Azharuddin, Joanne F. Liutkus, Jean‐François Yale, Farah Sultan, Ada Smith, Rose E. Otto, Diana Sherifali, Yan Yun Liu, Hertz
    Diabetes, Obesity and Metabolism.2023; 25(11): 3347.     CrossRef
  • Glucagon-like peptide-1 analog therapy in rare genetic diseases: monogenic obesity, monogenic diabetes, and spinal muscular atrophy
    Hussein Zaitoon, Ronit Lubetzky, Achiya Z. Amir, Hadar Moran-Lev, Liora Sagi, Michal Yacobi-Bach, Ophir Borger, Efrat Chorna, Yael Lebenthal, Avivit Brener
    Acta Diabetologica.2023; 60(8): 1099.     CrossRef
  • What can functional brain imaging teach us about remission of type 2 diabetes?
    Dhruti Hirani, Shahd Alabdulkader, Alexander. D. Miras, Victoria Salem
    Diabetic Medicine.2023;[Epub]     CrossRef
  • Fasting oxyntomodulin, glicentin, and gastric inhibitory polypeptide levels are associated with activation of reward‐ and attention‐related brain centres in response to visual food cues in adults with obesity: A cross‐sectional functional MRI study
    Nikolaos Perakakis, Olivia M. Farr, Christos S. Mantzoros
    Diabetes, Obesity and Metabolism.2021; 23(5): 1202.     CrossRef
  • Aberrant Brain Functional Connectivity Strength and Effective Connectivity in Patients with Type 2 Diabetes Mellitus
    Xi Guo, Su Wang, Yu-Chen Chen, Heng-Le Wei, Gang-Ping Zhou, Yu-Sheng Yu, Xindao Yin, Kun Wang, Hong Zhang, Eusebio Chiefari
    Journal of Diabetes Research.2021; 2021: 1.     CrossRef
Review
Molecular Mechanisms of Appetite Regulation
Ji Hee Yu, Min-Seon Kim
Diabetes Metab J. 2012;36(6):391-398.   Published online December 12, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.6.391
  • 11,222 View
  • 281 Download
  • 85 Crossref
AbstractAbstract PDFPubReader   

The prevalence of obesity has been rapidly increasing worldwide over the last several decades and has become a major health problem in developed countries. The brain, especially the hypothalamus, plays a key role in the control of food intake by sensing metabolic signals from peripheral organs and modulating feeding behaviors. To accomplish these important roles, the hypothalamus communicates with other brain areas such as the brainstem and reward-related limbic pathways. The adipocyte-derived hormone leptin and pancreatic β-cell-derived insulin inform adiposity to the hypothalamus. Gut hormones such as cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide 1, and oxyntomodulin transfer satiety signals to the brain and ghrelin relays hunger signals. The endocannabinoid system and nutrients are also involved in the physiological regulation of food intake. In this article, we briefly review physiological mechanisms of appetite regulation.

Citations

Citations to this article as recorded by  
  • Regulation of glycose and lipid metabolism and application based on the colloidal nutrition science properties of konjac glucomannan: A comprehensive review
    Pengkui Xia, Ying Zheng, Li Sun, Wenxin Chen, Longchen Shang, Jing Li, Tao Hou, Bin Li
    Carbohydrate Polymers.2024; 331: 121849.     CrossRef
  • Weight Regain after Metabolic Surgery: Beyond the Surgical Failure
    Juan Salazar, Pablo Duran, Bermary Garrido, Heliana Parra, Marlon Hernández, Clímaco Cano, Roberto Añez, Henry García-Pacheco, Gabriel Cubillos, Neidalis Vasquez, Maricarmen Chacin, Valmore Bermúdez
    Journal of Clinical Medicine.2024; 13(4): 1143.     CrossRef
  • Thylakoid supplementation and hunger and fullness perception: a systematic review and dose-response meta-analysis of randomized controlled trials
    Negin Nikrad, Mehdi Ghaffari Sarghein, Mahdieh Abbasalizad Farhangi
    Nutrition Reviews.2024;[Epub]     CrossRef
  • Stomach clusterin as a gut-derived feeding regulator
    Cherl NamKoong, Bohye Kim, Ji Hee Yu, Byung Soo Youn, Hanbin Kim, Evonne Kim, So Young Gil, Gil Myoung Kang, Chan Hee Lee, Young-Bum Kim, Kyeong-Han Park, Min-Seon Kim, Obin Kwon
    BMB Reports.2024; 57(3): 149.     CrossRef
  • Anorexigenic neuropeptides as anti-obesity and neuroprotective agents
    Veronika Strnadová, Andrea Pačesová, Vilém Charvát, Zuzana Šmotková, Blanka Železná, Jaroslav Kuneš, Lenka Maletínská
    Bioscience Reports.2024;[Epub]     CrossRef
  • UV Irradiation Increases Appetite and Prevents Body Weight Gain through the Upregulation of Norepinephrine in Mice
    Qing-Ling Quan, Eun Ju Kim, Sungsoo Kim, Yeon Kyung Kim, Min Hwa Chung, Yu-Dan Tian, Chang-Yup Shin, Dong Hun Lee, Jin Ho Chung
    Journal of Investigative Dermatology.2024; 144(10): 2273.     CrossRef
  • Current Evidence of Natural Products against Overweight and Obesity: Molecular Targets and Mechanisms of Action
    Cristina Alicia Elizalde-Romero, Nayely Leyva-López, Laura Aracely Contreras-Angulo, Rigoberto Cabanillas Ponce de-León, Libia Zulema Rodriguez-Anaya, Josefina León-Félix, J. Basilio Heredia, Saul Armando Beltrán-Ontiveros, Erick Paul Gutiérrez-Grijalva
    Receptors.2024; 3(3): 362.     CrossRef
  • The association between dietary habits and self-care behavior of pregnant women with pregnancy complications
    Mehdi Karimi, Maryam Mofidi Nejad, Razieh Tabaeifard, Noushin Omid, Zahra Rezaei, Leila Azadbakht
    Scientific Reports.2024;[Epub]     CrossRef
  • Addressing Obesity in Diabetes
    Melissa Magwire, Jacqueline Lamanna, Starlin Haydon-Greatting, Constance Brown-Riggs, Paulina Duker
    ADCES in Practice.2024; 12(6): 24.     CrossRef
  • Molecular mechanisms of zinc in alleviating obesity: Recent updates (Review)
    Ratih Yudhani, Dyonisa Pakha, Nanang Wiyono, Brian Wasita
    World Academy of Sciences Journal.2024;[Epub]     CrossRef
  • The non-conventional edible plant foroba (Parkia biglobosa) has anti-obesity effect, improves lipid peroxidation and reverses colon and hippocampal lesions in healthy and obese rats
    Mirela Gouveia-Nhanca, Maria Luiza Rolim Bezerra, Kamila Sabino Batista, Rafael Oliveira Pinheiro, Naís Lira Soares, Maria Carolina de Paiva Sousa, Adriano Francisco Alves, Mateus Duarte Ribeiro, Alexandre Sergio Silva, Marciane Magnani, Marcos dos Santos
    Journal of Functional Foods.2023; 108: 105745.     CrossRef
  • Aberrant bone marrow-derived microglia in the hypothalamus may dysregulate appetite in diabetes
    Miwako Katagi, Yuki Nakae, Junko Okano, Kazunori Fujino, Tomoki Tanaka, Itsuko Miyazawa, Natsuko Ohashi, Takahiko Nakagawa, Hideto Kojima
    Biochemical and Biophysical Research Communications.2023; 682: 132.     CrossRef
  • Proteins and peptides from vegetable food sources as therapeutic adjuvants for the type 2 diabetes mellitus
    Ivan Chan-Zapata, Carlos Sandoval-Castro, Maira Rubí Segura-Campos
    Critical Reviews in Food Science and Nutrition.2022; 62(10): 2673.     CrossRef
  • Differential effects of citalopram on the intake of high fat or high carbohydrates diets in female and male rats
    Amparo L. De la Fuente-Reynoso, Eliana Barrios De Tomasi, Jorge Juárez
    Nutritional Neuroscience.2022; 25(7): 1477.     CrossRef
  • Egzersizin iştah ve iştah hormonları üzerine etkisinin incelenmesi: PubMed üzerinden yapılmış sistematik derleme
    Esmanur Kaya, Şerife Vatansever
    Turkish Journal of Sports Medicine.2022; 57(1): 51.     CrossRef
  • Role of Leu72Met of GHRL and Gln223Arg of LEPR Variants on Food Intake, Subjective Appetite, and Hunger-Satiety Hormones
    Tania Sanchez-Murguia, Nathaly Torres-Castillo, Lisset Magaña-de la Vega, Saraí Citlalic Rodríguez-Reyes, Wendy Campos-Pérez, Erika Martínez-López
    Nutrients.2022; 14(10): 2100.     CrossRef
  • Appetite ratings and ghrelin concentrations in young adults after administration of a balanced meal. Does sex matter?
    Alessandro Leone, Ramona De Amicis, Marta Pellizzari, Simona Bertoli, Simone Ravella, Alberto Battezzati
    Biology of Sex Differences.2022;[Epub]     CrossRef
  • Interplay between fatty acid desaturase2 (FADS2) rs174583 genetic variant and dietary antioxidant capacity: cardio-metabolic risk factors in obese individuals
    Mahdieh Khodarahmi, Parisa Javidzade, Mahdieh Abbasalizad Farhangi, Ahmad Hashemzehi, Houman Kahroba
    BMC Endocrine Disorders.2022;[Epub]     CrossRef
  • Appetite-regulating hormones in bipolar disorder: A systematic review and meta-analysis
    Błażej Misiak, Krzysztof Kowalski, Bartłomiej Stańczykiewicz, Francesco Bartoli, Giuseppe Carrà, Jerzy Samochowiec, Agnieszka Samochowiec, Dorota Frydecka
    Frontiers in Neuroendocrinology.2022; 67: 101013.     CrossRef
  • Association of plasma brain-derived neurotrophic factor levels and frailty in community-dwelling older adults
    Eun Roh, Soon Young Hwang, Eyun Song, Min Jeong Park, Hye Jin Yoo, Sei Hyun Baik, Miji Kim, Chang Won Won, Kyung Mook Choi
    Scientific Reports.2022;[Epub]     CrossRef
  • Gut Hormones in Health and Obesity: The Upcoming Role of Short Chain Fatty Acids
    Habeeb Alhabeeb, Ali AlFaiz, Emad Kutbi, Dayel AlShahrani, Abdullah Alsuhail, Saleh AlRajhi, Nemer Alotaibi, Khalid Alotaibi, Saad AlAmri, Saleh Alghamdi, Naji AlJohani
    Nutrients.2021; 13(2): 481.     CrossRef
  • Asprosin ve Glikoz Metabolizması Üzerine Etkileri
    M. Gizem KESER, Nurhan ÜNÜSAN
    Turkish Journal of Diabetes and Obesity.2021; 5(1): 89.     CrossRef
  • Recent Advances in Understanding Peripheral Taste Decoding I: 2010 to 2020
    Jea Hwa Jang, Obin Kwon, Seok Jun Moon, Yong Taek Jeong
    Endocrinology and Metabolism.2021; 36(3): 469.     CrossRef
  • Association of increased abdominal adiposity at birth with altered ventral caudate microstructure
    Dawn X. P. Koh, Mya Thway Tint, Peter D. Gluckman, Yap Seng Chong, Fabian K. P. Yap, Anqi Qiu, Johan G. Eriksson, Marielle V. Fortier, Patricia P. Silveira, Michael J. Meaney, Ai Peng Tan
    International Journal of Obesity.2021; 45(11): 2396.     CrossRef
  • The Crosstalk Between Brain Mediators Regulating Food Intake Behavior in Birds: A Review
    Behrouz Rahmani, Elham Ghashghayi, Morteza Zendehdel, Mina Khodadadi, Behnam Hamidi
    International Journal of Peptide Research and Therapeutics.2021; 27(4): 2349.     CrossRef
  • Oral Semaglutide, the First Ingestible Glucagon-Like Peptide-1 Receptor Agonist: Could It Be a Magic Bullet for Type 2 Diabetes?
    Hwi Seung Kim, Chang Hee Jung
    International Journal of Molecular Sciences.2021; 22(18): 9936.     CrossRef
  • Potential Role of Hypothalamic and Plasma Ghrelin in the Feeding Behavior of Obese Type 2 Diabetic Rats with Intraventricular Glucagon-Like Peptide-1 Receptor Agonist Intervention
    Ke Lu, Xiaoyan Chen, Xuelian Deng, Juan Long, Jianhua Yan
    Obesity Facts.2021; 14(1): 10.     CrossRef
  • Managing obesity through natural polyphenols: A review
    Manisha Singh, Thilini Thrimawithana, Ravi Shukla, Benu Adhikari
    Future Foods.2020; 1-2: 100002.     CrossRef
  • Neurochemical Regulators of Food Behavior for Pharmacological Treatment of Obesity: Current Status and Future Prospects
    Gayane Sargis Vardanyan, Hasmik Samvel Harutyunyan, Michail Iosif Aghajanov, Ruben Sargis Vardanyan
    Future Medicinal Chemistry.2020; 12(20): 1865.     CrossRef
  • Modulation of feeding behavior and metabolism by dynorphin
    Aishwarya Ghule, Ildiko Rácz, Andras Bilkei-Gorzo, Este Leidmaa, Meike Sieburg, Andreas Zimmer
    Scientific Reports.2020;[Epub]     CrossRef
  • Possible role of peptide YY (PYY) in the pathophysiology of irritable bowel syndrome (IBS)
    Magdy El-Salhy, Jan Gunnar Hatlebakk, Trygve Hausken
    Neuropeptides.2020; 79: 101973.     CrossRef
  • Prolactin-releasing peptide increases food intake and affects hypothalamic physiology in Japanese quail (Coturnix japonica)
    B.R. McConn, T. Tachibana, E.R. Gilbert, M.A. Cline
    Domestic Animal Endocrinology.2020; 72: 106464.     CrossRef
  • Obesity induced by Borna disease virus in rats: key roles of hypothalamic fast-acting neurotransmitters and inflammatory infiltrates
    Georg Gosztonyi, Hanns Ludwig, Liv Bode, Moujahed Kao, Manfred Sell, Peter Petrusz, Béla Halász
    Brain Structure and Function.2020; 225(5): 1459.     CrossRef
  • D‐methionine improves cisplatin‐induced anorexia and dyspepsia syndrome by attenuating intestinal tryptophan hydroxylase 1 activity and increasing plasma leptin concentration
    Yi‐Sin Wong, Meei‐Yn Lin, Pei‐Fen Liu, Jiunn‐Liang Ko, Guan‐Ting Huang, Dom‐Gene Tu, Chu‐Chyn Ou
    Neurogastroenterology & Motility.2020;[Epub]     CrossRef
  • Effects of oral, smoked, and vaporized cannabis on endocrine pathways related to appetite and metabolism: a randomized, double-blind, placebo-controlled, human laboratory study
    Mehdi Farokhnia, Gray R. McDiarmid, Matthew N. Newmeyer, Vikas Munjal, Osama A. Abulseoud, Marilyn A. Huestis, Lorenzo Leggio
    Translational Psychiatry.2020;[Epub]     CrossRef
  • Role of Paraventricular Nucleus in Regulation of Feeding Behaviour and the Design of Intranuclear Neuronal Pathway Communications
    Shiba Yousefvand, Farshid Hamidi
    International Journal of Peptide Research and Therapeutics.2020; 26(3): 1231.     CrossRef
  • Self-Reported Eating Speed and Incidence of Gestational Diabetes Mellitus: the Japan Environment and Children’s Study
    Jia-Yi Dong, Satoyo Ikehara, Takashi Kimura, Meishan Cui, Yoko Kawanishi, Tadashi Kimura, Kimiko Ueda, Hiroyasu Iso
    Nutrients.2020; 12(5): 1296.     CrossRef
  • Effects of a high-fat-diet supplemented with probiotics and ω3-fatty acids on appetite regulatory neuropeptides and neurotransmitters in a pig model
    D. Valent, L. Arroyo, E. Fàbrega, M. Font-i-Furnols, M. Rodríguez-Palmero, J.A. Moreno-Muñoz, J. Tibau, A. Bassols
    Beneficial Microbes.2020; 11(4): 347.     CrossRef
  • Electro-Acupuncture Alleviates Cisplatin-Induced Anorexia in Rats by Modulating Ghrelin and Monoamine Neurotransmitters
    Ji Yun Baek, Tuy An Trinh, Wonsang Huh, Ji Hoon Song, Hyun Young Kim, Juhee Lim, Jinhee Kim, Hyun Jin Choi, Tae-Hun Kim, Ki Sung Kang
    Biomolecules.2019; 9(10): 624.     CrossRef
  • Interleukin-6 Expression by Hypothalamic Microglia in Multiple Inflammatory Contexts: A Systematic Review
    Vanessa C. D. Bobbo, Carlos P. Jara, Natália F. Mendes, Joseane Morari, Lício A. Velloso, Eliana P. Araújo
    BioMed Research International.2019; 2019: 1.     CrossRef
  • Abnormalities in Glucose Metabolism, Appetite-Related Peptide Release, and Pro-inflammatory Cytokines Play a Central Role in Appetite Disorders in Peritoneal Dialysis
    Lorena Avila-Carrasco, Mario A. Pavone, Elena González, Álvaro Aguilera-Baca, Rafael Selgas, Gloria del Peso, Secundino Cigarran, Manuel López-Cabrera, Abelardo Aguilera
    Frontiers in Physiology.2019;[Epub]     CrossRef
  • Branched chain amino acids stimulate gut satiety hormone cholecystokinin secretion through activation of the umami taste receptor T1R1/T1R3 using an in vitro porcine jejunum model
    Min Tian, Jinghui Heng, Hanqing Song, Yufeng Zhang, Fang Chen, Wutai Guan, Shihai Zhang
    Food & Function.2019; 10(6): 3356.     CrossRef
  • Multi-Omic Biological Age Estimation and Its Correlation With Wellness and Disease Phenotypes: A Longitudinal Study of 3,558 Individuals
    John C Earls, Noa Rappaport, Laura Heath, Tomasz Wilmanski, Andrew T Magis, Nicholas J Schork, Gilbert S Omenn, Jennifer Lovejoy, Leroy Hood, Nathan D Price, David Le Couteur
    The Journals of Gerontology: Series A.2019; 74(Supplement): S52.     CrossRef
  • The impact of sugar consumption on stress driven, emotional and addictive behaviors
    Angela Jacques, Nicholas Chaaya, Kate Beecher, Syed Aoun Ali, Arnauld Belmer, Selena Bartlett
    Neuroscience & Biobehavioral Reviews.2019; 103: 178.     CrossRef
  • Leptin Signaling in the Control of Metabolism and Appetite: Lessons from Animal Models
    Alberto A. Barrios-Correa, José A. Estrada, Irazú Contreras
    Journal of Molecular Neuroscience.2018; 66(3): 390.     CrossRef
  • Role of paraventricular hypothalamic dopaminergic D1 receptors in food intake regulation of food-deprived rats
    Zahra. Mirmohammadsadeghi, Masoud. Shareghi Brojeni, Abbas. Haghparast, Afsaneh. Eliassi
    European Journal of Pharmacology.2018; 818: 43.     CrossRef
  • Integrating Thyroid Hormone Signaling in Hypothalamic Control of Metabolism: Crosstalk Between Nuclear Receptors
    Soumaya Kouidhi, Marie-Stéphanie Clerget-Froidevaux
    International Journal of Molecular Sciences.2018; 19(7): 2017.     CrossRef
  • Review article: Role of satiety hormones in anorexia induction by Trichothecene mycotoxins
    Chloé Terciolo, Marc Maresca, Philippe Pinton, Isabelle P. Oswald
    Food and Chemical Toxicology.2018; 121: 701.     CrossRef
  • Obezite ve Ghrelin/Leptin İlişkisi
    Aliye Sağkan Öztürk, Abdullah ARPACI
    Mustafa Kemal Üniversitesi Tıp Dergisi.2018; 9(35): 136.     CrossRef
  • Overexpression of Wild-Type Human Alpha-Synuclein Causes Metabolism Abnormalities in Thy1-aSYN Transgenic Mice
    Elodie Cuvelier, Mathieu Méquinion, Coline Leghay, William Sibran, Aliçia Stievenard, Alessia Sarchione, Marie-Amandine Bonte, Christel Vanbesien-Mailliot, Odile Viltart, Kevin Saitoski, Emilie Caron, Alexandra Labarthe, Thomas Comptdaer, Pierre Semaille,
    Frontiers in Molecular Neuroscience.2018;[Epub]     CrossRef
  • Aetiology of eating behaviours: A possible mechanism to understand obesity development in early childhood
    Nikki Boswell, Rebecca Byrne, Peter S.W. Davies
    Neuroscience & Biobehavioral Reviews.2018; 95: 438.     CrossRef
  • Clinical Phenotype of Depression Affects Interleukin-6 Synthesis
    Łukasz Zadka, Piotr Dzięgiel, Michał Kulus, Marcin Olajossy
    Journal of Interferon & Cytokine Research.2017; 37(6): 231.     CrossRef
  • Altered Adipogenesis in Zebrafish Larvae Following High Fat Diet and Chemical Exposure Is Visualised by Stimulated Raman Scattering Microscopy
    Marjo Den Broeder, Miriam Moester, Jorke Kamstra, Peter Cenijn, Valentina Davidoiu, Leonie Kamminga, Freek Ariese, Johannes De Boer, Juliette Legler
    International Journal of Molecular Sciences.2017; 18(4): 894.     CrossRef
  • SIFamide Translates Hunger Signals into Appetitive and Feeding Behavior in Drosophila
    Carlotta Martelli, Ulrike Pech, Simon Kobbenbring, Dennis Pauls, Britta Bahl, Mirjam Vanessa Sommer, Atefeh Pooryasin, Jonas Barth, Carmina Warth Perez Arias, Chrystalleni Vassiliou, Abud Jose Farca Luna, Haiko Poppinga, Florian Gerhard Richter, Christian
    Cell Reports.2017; 20(2): 464.     CrossRef
  • Effect of Mulberry Extract on the Lipid Profile and Liver Function in Mice Fed a High Fat Diet
    Kyung-Soon Choi, Yong-Hwan Kim, Kyung-Ok Shin
    The Korean Journal of Food And Nutrition.2016; 29(3): 411.     CrossRef
  • Helicobacter pylori Infection in Children: Nutritional Status and Associations with Serum Leptin, Ghrelin, and IGF‐1 Levels
    Gulin Erdemir, Tanju Basarir Ozkan, Taner Ozgur, Derya Altay, Sinan Cavun, Guher Goral
    Helicobacter.2016; 21(4): 317.     CrossRef
  • Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction
    Fang Sun, Shiqiang Xiong, Zhiming Zhu
    Nutrients.2016; 8(5): 174.     CrossRef
  • Effects of Short-Term Exenatide Treatment on Regional Fat Distribution, Glycated Hemoglobin Levels, and Aortic Pulse Wave Velocity of Obese Type 2 Diabetes Mellitus Patients
    Ju-Young Hong, Keun-Young Park, Byung-Joon Kim, Won-Min Hwang, Dong-Ho Kim, Dong-Mee Lim
    Endocrinology and Metabolism.2016; 31(1): 80.     CrossRef
  • The role of the neuropeptide Y (NPY) family in the pathophysiology of inflammatory bowel disease (IBD)
    Magdy El-Salhy, Trygve Hausken
    Neuropeptides.2016; 55: 137.     CrossRef
  • Proactive and Progressive Approaches in Managing Obesity
    Robert H. Eckel, Harold E. Bays, Samuel Klein, Deborah Bade Horn
    Postgraduate Medicine.2016; 128(sup1): 21.     CrossRef
  • The role of food intake regulating peptides in cardiovascular regulation
    B. Mikulášková, L. Maletínská, J. Zicha, J. Kuneš
    Molecular and Cellular Endocrinology.2016; 436: 78.     CrossRef
  • Altered gut and adipose tissue hormones in overweight and obese individuals: cause or consequence?
    M E J Lean, D Malkova
    International Journal of Obesity.2016; 40(4): 622.     CrossRef
  • Expression of NUCB2/nesfatin-1 in the taste buds of rats
    Xun Cao, Xiao Zhou, Yang Cao, Xiao-Min Liu, Li-Hong Zhou
    Endocrine Journal.2016; 63(1): 37.     CrossRef
  • Brain Regulation of Energy Metabolism
    Eun Roh, Min-Seon Kim
    Endocrinology and Metabolism.2016; 31(4): 519.     CrossRef
  • Stopped-Flow Studies of the Reduction of the Copper Centers Suggest a Bifurcated Electron Transfer Pathway in Peptidylglycine Monooxygenase
    Shefali Chauhan, Parisa Hosseinzadeh, Yi Lu, Ninian J. Blackburn
    Biochemistry.2016; 55(13): 2008.     CrossRef
  • Potential role of bioactive compounds of Phaseolus vulgaris L. on lipid-lowering mechanisms
    Aurea K. Ramírez-Jiménez, Rosalía Reynoso-Camacho, M. Elizabeth Tejero, Fabiola León-Galván, Guadalupe Loarca-Piña
    Food Research International.2015; 76: 92.     CrossRef
  • Recent developments in the pathophysiology of irritable bowel syndrome
    Magdy El-Salhy
    World Journal of Gastroenterology.2015; 21(25): 7621.     CrossRef
  • Lifestyle Changes Followed by Bariatric Surgery Lower Inflammatory Markers and the Cardiovascular Risk Factors C3 and C4
    Torunn Kristin Nestvold, Erik Waage Nielsen, Judith Krey Ludviksen, Hilde Fure, Anne Landsem, Knut Tore Lappegård
    Metabolic Syndrome and Related Disorders.2015; 13(1): 29.     CrossRef
  • Diet in irritable bowel syndrome
    Magdy El-Salhy, Doris Gundersen
    Nutrition Journal.2015;[Epub]     CrossRef
  • 3p22.1p21.31 microdeletion identifies CCK as Asperger syndrome candidate gene and shows the way for therapeutic strategies in chromosome imbalances
    Ivan Y. Iourov, Svetlana G. Vorsanova, Victoria Y. Voinova, Yuri B. Yurov
    Molecular Cytogenetics.2015;[Epub]     CrossRef
  • The effect of slow spaced eating on hunger and satiety in overweight and obese patients with type 2 diabetes mellitus
    Theodoros Angelopoulos, Alexander Kokkinos, Christos Liaskos, Nicholas Tentolouris, Kleopatra Alexiadou, Alexander Dimitri Miras, Iordanis Mourouzis, Despoina Perrea, Constantinos Pantos, Nicholas Katsilambros, Stephen R Bloom, Carel Wynard le Roux
    BMJ Open Diabetes Research & Care.2014; 2(1): e000013.     CrossRef
  • Bisphenol A is related to circulating levels of adiponectin, leptin and ghrelin, but not to fat mass or fat distribution in humans
    Monika Rönn, Lars Lind, Jan Örberg, Joel Kullberg, Stefan Söderberg, Anders Larsson, Lars Johansson, Håkan Ahlström, P. Monica Lind
    Chemosphere.2014; 112: 42.     CrossRef
  • The modulatory role of alpha-melanocyte stimulating hormone administered spinally in the regulation of blood glucose level in d-glucose-fed and restraint stress mouse models
    Yun-Beom Sim, Soo-Hyun Park, Sung-Su Kim, Su-Min Lim, Jun-Sub Jung, Hong-Won Suh
    Neuropeptides.2014; 48(4): 207.     CrossRef
  • The forgotten members of the glucagon family
    Dominique Bataille, Stéphane Dalle
    Diabetes Research and Clinical Practice.2014; 106(1): 1.     CrossRef
  • Incretin mimetics as pharmacologic tools to elucidate and as a new drug strategy to treat traumatic brain injury
    Nigel H. Greig, David Tweedie, Lital Rachmany, Yazhou Li, Vardit Rubovitch, Shaul Schreiber, Yung-Hsiao Chiang, Barry J. Hoffer, Jonathan Miller, Debomoy K. Lahiri, Kumar Sambamurti, Robert E. Becker, Chaim G. Pick
    Alzheimer's & Dementia.2014;[Epub]     CrossRef
  • Fatty acid analysis and regulatory effects of citron (Citrus junosSieb. ex TANAKA) seed oil on nitric oxide production, lipid accumulation, and leptin secretion
    Tae Woo Kim, Kyoung Kon Kim, Yun Hwan Kang, Dae Jung Kim, Myeon Choe
    Journal of Nutrition and Health.2014; 47(4): 221.     CrossRef
  • Analysis of Pine Nut Oil Composition and Its Effects on Obesity
    Kyoung Kon Kim, Yun Hwan Kang, Dae Jung Kim, Tae Woo Kim, Myeon Choe
    Korean Journal of Food Science and Technology.2014; 46(5): 630.     CrossRef
  • Anti-obesity effects of KR-66195, a synthetic DPP-IV inhibitor, in diet-induced obese mice and obese-diabetic ob/ob mice
    Eun Young Lee, Yeon Wook Kim, Hyunhee Oh, Cheol Soo Choi, Jin Hee Ahn, Byung-Wan Lee, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee
    Metabolism.2014; 63(6): 793.     CrossRef
  • Position and Length of Fatty Acids Strongly Affect Receptor Selectivity Pattern of Human Pancreatic Polypeptide Analogues
    Veronika Mäde, Kathrin Bellmann‐Sickert, Anette Kaiser, Jens Meiler, Annette G. Beck‐Sickinger
    ChemMedChem.2014; 9(11): 2463.     CrossRef
  • Regulation of food intake after surgery and the gut brain axis
    Nilanjana Tewari, Sherif Awad, Dileep N. Lobo
    Current Opinion in Clinical Nutrition and Metabolic Care.2013; 16(5): 569.     CrossRef
  • Effect of ambient temperature during acute aerobic exercise on short-term appetite, energy intake, and plasma acylated ghrelin in recreationally active males
    Lucy K. Wasse, James A. King, David J. Stensel, Caroline Sunderland
    Applied Physiology, Nutrition, and Metabolism.2013; 38(8): 905.     CrossRef
  • Peripheral Pathways in the Food-Intake Control towards the Adipose-Intestinal Missing Link
    Hugo Mendieta Zerón, Ma. Victoria Domínguez García, María del Socorro Camarillo Romero, Miriam V. Flores-Merino
    International Journal of Endocrinology.2013; 2013: 1.     CrossRef
  • Alteration of sweet taste in high-fat diet induced obese rats after 4 weeks treatment with exenatide
    Xiao-juan Zhang, Yu-qing Wang, Yang Long, Lei Wang, Yun Li, Fa-bao Gao, Hao-ming Tian
    Peptides.2013; 47: 115.     CrossRef
  • Decrease of Obesity by Allantoin via Imidazoline I1-Receptor Activation in High Fat Diet-Fed Mice
    Hsien-Hui Chung, Kung Shing Lee, Juei-Tang Cheng
    Evidence-Based Complementary and Alternative Medicine.2013; 2013: 1.     CrossRef
  • Hunger Hormone Profile Monitoring after Gastroplication in an Adolescent
    Valeria Calcaterra, Gloria Pelizzo, Ghassan Nakib, Daniela Larizza, Maria Luisa Fonte, Mara De Amici, Hellas Cena
    Hormone Research in Paediatrics.2013; 80(3): 213.     CrossRef
Original Articles
Intracerebroventricular Injection of Metformin Induces Anorexia in Rats
Chang Koo Lee, Yoon Jung Choi, So Young Park, Jong Yeon Kim, Kyu Chang Won, Yong Woon Kim
Diabetes Metab J. 2012;36(4):293-299.   Published online August 20, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.4.293
  • 5,220 View
  • 45 Download
  • 28 Crossref
AbstractAbstract PDFPubReader   
Background

Metformin, an oral biguanide insulin-sensitizing agent, is well known to decrease appetite. Although there is evidence that metformin could affect the brain directly, the exact mechanism is not yet known.

Methods

To evaluate whether metformin induces anorexia via the hypothalamus, various concentrations of metformin were injected into the lateral ventricle of rats through a chronically implanted catheter and food intake was measured for 24 hours. The hypothalamic neuropeptides associated with regulation of food intake were also analyzed following 1 hour of intracerebroventricular (ICV) injections of metformin.

Results

An ICV injection of metformin decreased food intake in a dose-dependent manner in unrestrained conscious rats. Hypothalamic phosphorylated AMP-activated protein kinase (pAMPK) increased by 3 µg with metformin treatment, but there was no further increase in pAMPK with increases in metformin dosage. The hypothalamic phosphorylated signal transducer and activator of transcription 3 (pSTAT3) increased by 3 µg with metformin treatment, but, there was no further increase in pSTAT3 level following increases of metformin dosage. Hypothalamic proopiomelanocortin was elevated with metformin treatment, while neuropeptide Y was not significantly changed.

Conclusion

Our results suggest that metformin induces anorexia via direct action in the hypothalamus and the increase in pSTAT3, at least in part, is involved in the process. However, hypothalamic pAMPK appears not to contribute to metformin-induced appetite reduction in normal rats. Further studies exploring new pathways connecting metformin and feeding regulation are needed.

Citations

Citations to this article as recorded by  
  • TRPV1: A novel target for the therapy of diabetes and diabetic complications
    Yu-rong Shen, Long Cheng, Dong-fang Zhang
    European Journal of Pharmacology.2024; 984: 177021.     CrossRef
  • Metabolic and Metabolomic Effects of Metformin in Murine Model of Pulmonary Adenoma Formation
    Andrew C. Elton, Vannesa Cedarstrom, Arman Quraishi, Beverly Wuertz, Kevin Murray, Todd W. Markowski, Donna Seabloom, Frank G. Ondrey
    Nutrition and Cancer.2023; 75(3): 1014.     CrossRef
  • Steroidogenic Effect of Luteinizing Hormone Receptor Agonists and Metformin in Male Rats with Androgenic Deficiency Caused by Diet-Induced Obesity
    A. A. Bakhtyukov, K. V. Derkach, I. A. Lebedev, V. N. Sorokoumov, A. O. Shpakov
    Journal of Evolutionary Biochemistry and Physiology.2023; 59(5): 1810.     CrossRef
  • Steroidogenic Effect of Luteinizing Hormone Receptor Agonists and Metformin in Male Rats with Androgenic Deficiency Caused by Diet-Induced Obesity
    A. A. Bakhtyukov, K. V. Derkach, I. A. Lebedev, V. N. Sorokoumov, A. O. Shpakov
    Российский физиологический журнал им  И  М  Сеченова.2023; 109(10): 1414.     CrossRef
  • Metformin in nucleus accumbens core reduces cue‐induced cocaine seeking in male and female rats
    Amy Chan, Alexis Willard, Sarah Mulloy, Noor Ibrahim, Allegra Sciaccotta, Mark Schonfeld, Sade M. Spencer
    Addiction Biology.2022;[Epub]     CrossRef
  • Knockdown of Endogenous Nucb2/Nesfatin-1 in the PVN Leads to Obese-Like Phenotype and Abolishes the Metformin- and Stress-Induced Thermogenic Response in Rats
    Daniel Stephan, Natalie Taege, Riccardo Dore, Julica Folberth, Olaf Jöhren, Markus Schwaninger, Hendrik Lehnert, Carla Schulz
    Hormone and Metabolic Research.2022; 54(11): 768.     CrossRef
  • Modulation of hypothalamic AMPK phosphorylation by olanzapine controls energy balance and body weight
    Vitor Ferreira, Cintia Folgueira, Maria Guillén, Pablo Zubiaur, Marcos Navares, Assel Sarsenbayeva, Pilar López-Larrubia, Jan W. Eriksson, Maria J. Pereira, Francisco Abad-Santos, Guadalupe Sabio, Patricia Rada, Ángela M. Valverde
    Metabolism.2022; 137: 155335.     CrossRef
  • Metformin acts on the gut-brain axis to ameliorate antipsychotic-induced metabolic dysfunction
    Xiaorong Wang, Huimin Huang, Yiyi Zhu, Shaoli Li, Peifen Zhang, Jiajun Jiang, Caixi Xi, Lingling Wu, Xingle Gao, Yaoyang Fu, Danhua Zhang, Yiqing Chen, Shaohua Hu, Jianbo Lai
    BioScience Trends.2021; 15(5): 321.     CrossRef
  • Therapeutic effect of treatment with metformin and/or 4-hydroxychalcone in male Wistar rats with nonalcoholic fatty liver disease
    Selene de Jesús Acosta-Cota, Elsa Maribel Aguilar-Medina, Rosalío Ramos-Payán, José Guadalupe Rendón Maldonado, José Geovanni Romero-Quintana, Julio Montes-Avila, Juan I. Sarmiento-Sánchez, Carolina Gabriela Plazas-Guerrero, Marcela J. Vergara-Jiménez, Ar
    European Journal of Pharmacology.2019; 863: 172699.     CrossRef
  • The evidence of metabolic-improving effect of metformin in Ay/a mice with genetically-induced melanocortin obesity and the contribution of hypothalamic mechanisms to this effect
    Kira Derkach, Irina Zakharova, Inna Zorina, Andrey Bakhtyukov, Irina Romanova, Liubov Bayunova, Alexander Shpakov, Guillermo López Lluch
    PLOS ONE.2019; 14(3): e0213779.     CrossRef
  • Effect of Metformin on Antipsychotic-Induced Metabolic Dysfunction: The Potential Role of Gut-Brain Axis
    Chao Luo, Xu Wang, Hanxue Huang, Xiaoyuan Mao, Honghao Zhou, Zhaoqian Liu
    Frontiers in Pharmacology.2019;[Epub]     CrossRef
  • Metformin alters signaling induced crosstalk and homeostasis in the carcinogenesis paradigm “Epistemology of the origin of cancer”
    Björn L.D.M. Brücher, Ijaz S. Jamall, Obul R. Bandapalli
    4open.2019; 2: 12.     CrossRef
  • Melatonin potentiates the effects of metformin on glucose metabolism and food intake in high‐fat‐fed rats
    Rosana F. Dantas‐Ferreira, Helene Raingard, Stephanie Dumont, Carole Schuster‐Klein, Beatrice Guardiola‐Lemaitre, Paul Pevet, Etienne Challet
    Endocrinology, Diabetes & Metabolism.2018;[Epub]     CrossRef
  • Molecular Mechanisms of the Effects of Metformin on the Functional Activity of Brain Neurons
    A. O. Shpakov, K. V. Derkach
    Neuroscience and Behavioral Physiology.2018; 48(8): 969.     CrossRef
  • Effect of Metformin/Irinotecan-Loaded Poly-Lactic-Co-Glycolic Acid Nanoparticles on Glioblastoma: In Vitro and In Vivo Studies
    Ali Taghizadehghalehjoughi, Ahmet Hacimuftuoglu, Meltem Cetin, Afife Busra Ugur, Bianca Galateanu, Yaroslav Mezhuev, Ufuk Okkay, Numan Taspinar, Mehmet Taspinar, Abdullah Uyanik, Betul Gundogdu, Maryam Mohammadzadeh, Kemal Alp Nalci, Polychronis Stivaktak
    Nanomedicine.2018; 13(13): 1595.     CrossRef
  • Effect of Betahistine and Metformin on Antipsychotic-Induced Weight Gain: An Analysis of Two Clinical Trials
    Dongyu Kang, Zhihui Jing, Ranran Li, Gangrui Hei, Tiannan Shao, Li Li, Mengxi Sun, Ye Yang, Ying Wang, Xiaoyi Wang, Yujun Long, Xiansheng Huang, Renrong Wu
    Frontiers in Psychiatry.2018;[Epub]     CrossRef
  • Metformin: not only per os
    Lev M. Berstein
    Expert Review of Endocrinology & Metabolism.2018; 13(2): 63.     CrossRef
  • МЕТАБОЛИЧЕСКИЕ ПОКАЗАТЕЛИ И ФУНКЦИОНАЛЬНОЕ СОСТОЯНИЕ СИГНАЛЬНЫХ СИСТЕМ ГИПОТАЛАМУСА И ВЛИЯНИЕ НА НИХ МЕТФОРМИНА У МЫШЕЙ С МУТАЦИЕЙ AY/A, ГЕНЕТИЧЕСКИ ПРЕДРАСПОЛОЖЕННЫХ К ОЖИРЕНИЮ, "Доклады Академии наук"
    К.В. Деркач, И.О. Захарова, И.В. Романова, И. И. Зорина, А.Л. Михрина, А.О. Шпаков
    Доклады Академии Наук.2017; (4): 488.     CrossRef
  • Beneficial effects of metformin on energy metabolism and visceral fat volume through a possible mechanism of fatty acid oxidation in human subjects and rats
    Ichiro Tokubuchi, Yuji Tajiri, Shimpei Iwata, Kento Hara, Nobuhiko Wada, Toshihiko Hashinaga, Hitomi Nakayama, Hiroharu Mifune, Kentaro Yamada, M. Faadiel Essop
    PLOS ONE.2017; 12(2): e0171293.     CrossRef
  • Metabolic parameters and functional state of hypothalamic signaling systems in AY/a mice with genetic predisposition to obesity and the effect of metformin
    K. V. Derkach, I. O. Zakharova, I. V. Romanova, I. I. Zorina, A. L. Mikhrina, A. O. Shpakov
    Doklady Biochemistry and Biophysics.2017; 477(1): 377.     CrossRef
  • Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older C57BL/6J mice
    Joanne S. Allard, Evelyn J. Perez, Koji Fukui, Priscilla Carpenter, Donald K. Ingram, Rafael de Cabo
    Behavioural Brain Research.2016; 301: 1.     CrossRef
  • Intracerebroventricular Metformin Decreases Body Weight But Has Pro-oxidant Effects and Decreases Survival
    Luis Valmor Portela, Jussania Gnoatto, Andressa Wigner Brochier, Clarissa Branco Haas, Adriano Martimbianco de Assis, Afonso Kopczynski de Carvalho, Gisele Hansel, Eduardo Rigon Zimmer, Jean Pierre Oses, Alexandre Pastoris Muller
    Neurochemical Research.2015; 40(3): 514.     CrossRef
  • Metformin alleviates hepatosteatosis by restoring SIRT1-mediated autophagy induction via an AMP-activated protein kinase-independent pathway
    Young Mi Song, Yong-ho Lee, Ji-Won Kim, Dong-Sik Ham, Eun-Seok Kang, Bong Soo Cha, Hyun Chul Lee, Byung-Wan Lee
    Autophagy.2015; 11(1): 46.     CrossRef
  • Activation of AMP-activated protein kinase by metformin protects against global cerebral ischemia in male rats: Interference of AMPK/PGC-1α pathway
    Ghorbangol Ashabi, Fariba Khodagholi, Leila Khalaj, Mahdi Goudarzvand, Masoumeh Nasiri
    Metabolic Brain Disease.2014; 29(1): 47.     CrossRef
  • Acute oral metformin enhances satiation and activates brainstem nesfatinergic neurons
    Thaïs Rouquet, Pierre Clément, Stéphanie Gaigé, Catherine Tardivel, Julien Roux, Michel Dallaporta, Bruno Bariohay, Jean-Denis Troadec, Bruno Lebrun
    Obesity.2014; : n/a.     CrossRef
  • Metformin—mode of action and clinical implications for diabetes and cancer
    Ida Pernicova, Márta Korbonits
    Nature Reviews Endocrinology.2014; 10(3): 143.     CrossRef
  • Effects of metformin on weight loss
    Steven K. Malin, Sangeeta R. Kashyap
    Current Opinion in Endocrinology, Diabetes & Obesity.2014; 21(5): 323.     CrossRef
  • The effect of ghrelin on MK-801 induced memory impairment in rats
    Fatemeh Goshadrou, Mojtaba Kermani, Abdolaziz Ronaghi, Samad Sajjadi
    Peptides.2013; 44: 60.     CrossRef
ATP-Sensitive Potassium Channel-Deficient Mice Show Hyperphagia but Are Resistant to Obesity
Yeul Bum Park, Yun Jung Choi, So Young Park, Jong Yeon Kim, Seong Ho Kim, Dae Kyu Song, Kyu Chang Won, Yong Woon Kim
Diabetes Metab J. 2011;35(3):219-225.   Published online June 30, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.3.219
  • 4,128 View
  • 35 Download
  • 14 Crossref
AbstractAbstract PDFPubReader   
Background

The hypothalamus, the center for body weight regulation, can sense changes in blood glucose level based on ATP-sensitive potassium (KATP) channels in the hypothalamic neurons. We hypothesized that a lack of glucose sensing in the hypothalamus affects the regulations of appetite and body weight.

Methods

To evaluate this hypothesis, the responses to glucose loading and high fat feeding for eight weeks were compared in Kir6.2 knock-out (KO) mice and control C57BL/6 mice, because Kir6.2 is a key component of the KATP channel.

Results

The hypothalamic neuropeptide Y (NPY) analyzed one hour after glucose injection was suppressed in C57BL/6 mice, but not in Kir6.2 KO mice, suggesting a blunted hypothalamic response to glucose in Kir6.2 KO mice. The hypothalamic NPY expression at a fed state was elevated in Kir6.2 KO mice and was accompanied with hyperphagia. However, the retroperitoneal fat mass was markedly decreased in Kir6.2 KO mice compared to that in C57BL/6 mice. Moreover, the body weight and visceral fat following eight weeks of high fat feeding in Kir6.2 KO mice were not significantly different from those in control diet-fed Kir6.2 KO mice, while body weight and visceral fat mass were elevated due to high fat feeding in C57BL/6 mice.

Conclusion

These results suggested that Kir6.2 KO mice showed a blunted hypothalamic response to glucose loading and elevated hypothalamic NPY expression accompanied with hyperphagia, while visceral fat mass was decreased, suggesting resistance to diet-induced obesity. Further study is needed to explain this phenomenon.

Citations

Citations to this article as recorded by  
  • 17β-estradiol promotes acute refeeding in hungry mice via membrane-initiated ERα signaling
    Kaifan Yu, Yanlin He, Ilirjana Hyseni, Zhou Pei, Yongjie Yang, Pingwen Xu, Xing Cai, Hesong Liu, Na Qu, Hailan Liu, Yang He, Meng Yu, Chen Liang, Tingting Yang, Julia Wang, Pierre Gourdy, Jean-Francois Arnal, Francoise Lenfant, Yong Xu, Chunmei Wang
    Molecular Metabolism.2020; 42: 101053.     CrossRef
  • Brain Glucose-Sensing Mechanism and Energy Homeostasis
    A. J. López-Gambero, F. Martínez, K. Salazar, M. Cifuentes, F. Nualart
    Molecular Neurobiology.2019; 56(2): 769.     CrossRef
  • The involvement of purinergic signalling in obesity
    Geoffrey Burnstock, Daniela Gentile
    Purinergic Signalling.2018; 14(2): 97.     CrossRef
  • High‐fat‐diet‐induced remission of diabetes in a subset of KATP‐GOF insulin‐secretory‐deficient mice
    Zihan Yan, Zeenat A. Shyr, Manuela Fortunato, Alecia Welscher, Mariana Alisio, Michael Martino, Brian N. Finck, Hannah Conway, Maria S. Remedi
    Diabetes, Obesity and Metabolism.2018; 20(11): 2574.     CrossRef
  • Hypothalamic arcuate nucleus glucokinase regulates insulin secretion and glucose homeostasis
    Yue Ma, Risheka Ratnasabapathy, Chioma Izzi‐Engbeaya, Marie‐Sophie Nguyen‐Tu, Errol Richardson, Sufyan Hussain, Ivan De Backer, Christopher Holton, Mariana Norton, Gaelle Carrat, Blanche Schwappach, Guy A. Rutter, Waljit S. Dhillo, James Gardiner
    Diabetes, Obesity and Metabolism.2018; 20(9): 2246.     CrossRef
  • Overexpression of WNK1 in POMC-expressing neurons reduces weigh gain via WNK4-mediated degradation of Kir6.2
    Woo Young Chung, Jung Woo Han, Woon Heo, Min Goo Lee, Joo Young Kim
    Molecular and Cellular Biochemistry.2018; 447(1-2): 165.     CrossRef
  • Insights into the role of neuronal glucokinase
    Ivan De Backer, Sufyan S. Hussain, Stephen R. Bloom, James V. Gardiner
    American Journal of Physiology-Endocrinology and Metabolism.2016; 311(1): E42.     CrossRef
  • Obesogenic and Diabetogenic Effects of High-Calorie Nutrition Require Adipocyte BK Channels
    Julia Illison, Lijun Tian, Heather McClafferty, Martin Werno, Luke H. Chamberlain, Veronika Leiss, Antonia Sassmann, Stefan Offermanns, Peter Ruth, Michael J. Shipston, Robert Lukowski
    Diabetes.2016; 65(12): 3621.     CrossRef
  • ABCC8 R1420H Loss-of-Function Variant in a Southwest American Indian Community: Association With Increased Birth Weight and Doubled Risk of Type 2 Diabetes
    Leslie J. Baier, Yunhua Li Muller, Maria Sara Remedi, Michael Traurig, Paolo Piaggi, Gregory Wiessner, Ke Huang, Alyssa Stacy, Sayuko Kobes, Jonathan Krakoff, Peter H. Bennett, Robert G. Nelson, William C. Knowler, Robert L. Hanson, Colin G. Nichols, Clif
    Diabetes.2015; 64(12): 4322.     CrossRef
  • Glucokinase activity in the arcuate nucleus regulates glucose intake
    Syed Hussain, Errol Richardson, Yue Ma, Christopher Holton, Ivan De Backer, Niki Buckley, Waljit Dhillo, Gavin Bewick, Shuai Zhang, David Carling, Steve Bloom, James Gardiner
    Journal of Clinical Investigation.2015; 125(1): 337.     CrossRef
  • Dissecting the Etiology of Type 2 Diabetes in the Pima Indian Population
    Ewan R. Pearson
    Diabetes.2015; 64(12): 3993.     CrossRef
  • Ocular Hypotensive Effects of the ATP-Sensitive Potassium Channel Opener Cromakalim in Human and Murine Experimental Model Systems
    Uttio Roy Chowdhury, Cindy K. Bahler, Bradley H. Holman, Peter I. Dosa, Michael P. Fautsch, Ted S Acott
    PLOS ONE.2015; 10(11): e0141783.     CrossRef
  • Differential gene expression pattern in hypothalamus of chickens during fasting-induced metabolic reprogramming: Functions of glucose and lipid metabolism in the feed intake of chickens
    Xin-Ling Fang, Xiao-Tong Zhu, Sheng-Feng Chen, Zhi-Qi Zhang, Qing-Jie Zeng, Lin Deng, Jian-Long Peng, Jian-Jian Yu, Li-Na Wang, Song-Bo Wang, Ping Gao, Qing-Yan Jiang, Gang Shu
    Poultry Science.2014; 93(11): 2841.     CrossRef
  • Combined Treatment of Betulinic Acid, a PTP1B Inhibitor, with Orthosiphon stamineus Extract Decreases Body Weight in High-Fat–Fed Mice
    Yoon-Jung Choi, So-Young Park, Jong-Yeon Kim, Kyu-Chang Won, Bo-Ra Kim, Jong-Keun Son, Seung-Ho Lee, Yong-Woon Kim
    Journal of Medicinal Food.2013; 16(1): 2.     CrossRef

Diabetes Metab J : Diabetes & Metabolism Journal
Close layer
TOP