Diabetes & Metabolism Journal

Original Articles

Basic and Translational Research
Sleeve Gastrectomy with Fundoplication Enhances Metabolic Health in Obese Rats via Ghrelin Pathway Modulation and Multi-Organ Regulation: Xin Li, Aikebaier Aili, Yusujiang Tusuntuoheti, Yusunjiang Aierken, Kelimu Abudureyimu, Weihui Liu; Received May 4, 2025 Accepted November 23, 2025 Published online January 15, 2026; DOI: https://doi.org/10.4093/dmj.2025.0392 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Obesity serves as a predominant factor in the progression of metabolic syndrome and type 2 diabetes mellitus. While sleeve gastrectomy (SG) is a well-established surgical intervention, its impact on appetite-regulating hormones, such as ghrelin (GHRL), is limited. Sleeve gastrectomy combined with fundoplication (SGFD) has emerged as a potential strategy to improve metabolic outcomes by modifying both gastric anatomy and gut-brain signaling.
Methods
Sixty-five Sprague-Dawley rats were enrolled. After 8 weeks of high-fat feeding, 48 rats developed diet-induced obesity (DIO). These rats were randomized into four experimental groups: DIO control, sham-operated, SG, and SGFD, alongside a normal control cohort. Biochemical indicators, hormonal fluctuations, and insulin responsiveness were analyzed. Molecular expressions were evaluated through quantitative real-time polymerase chain reaction and Western blotting.
Results
SGFD reduced body weight (−24.7%), food intake (−28.3%), fasting glucose (−37.5%), triglycerides (−42.6%), and serum GHRL (−51.2%) compared with the DIO group (P<0.01). Gastric GHRL, preproghrelin, and ghrelin O-acyltransferase (GOAT) expression were suppressed. Hypothalamic neuropeptide Y (NPY) was downregulated, and AMP-activated protein kinase (AMPK) signaling was robustly enhanced across various tissues. SGFD also improved insulin receptor substrate-1 (IRS-1), glucose transporter type 4 (GLUT4), β-cell function, hepatic lipid oxidation, and brown adipose thermogenesis. SGFD outperformed SG in most metabolic and molecular outcomes (P<0.05).
Conclusion
SGFD provides superior metabolic benefits over SG alone by suppressing GHRL signaling and activating systemic AMPK pathways. SGFD represents a promising surgical strategy for obesity and metabolic syndrome.

Basic and Translational Research
Hepatocyte RAP1A Deletion Impairs Lipid Catabolism and Worsens Steatosis via Autophagy Activation: Xiujuan Wei, Yinxu Fu, Yu Fang, Xi Lin, Zhonggui Luo, Keyi Li, Kaiqiang Yang, Ting Fu, Liqin Jin, Jianxin Lyu, Qiongya Zhao; Diabetes Metab J. 2026;50(5):921-937. Published online November 24, 2025; DOI: https://doi.org/10.4093/dmj.2025.0388

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Abstract PDF Supplementary Material PubReader ePub: Background
Metabolic disorders such as obesity, type 2 diabetes mellitus, and fatty liver disease are often linked to excessive hepatic lipid accumulation. This study aimed to determine the role of Ras-related protein 1a (RAP1A) in regulating hepatic lipid metabolism and to elucidate how RAP1A impacts metabolic dysfunction-associated fatty liver disease progression. We focused on RAP1A’s influence on liver lipid homeostasis and its connection to metabolic health.
Methods
A liver-specific Rap1a knockout (LKO) mouse model was generated and fed a high-fat diet to induce obesity and steatosis. Metabolic phenotyping (body weight, adiposity, glucose tolerance, insulin sensitivity) and liver analyses (histology, triglyceride/ cholesterol content, and gene expression profiling) were performed. In parallel, cultured hepatocyte models (alpha mouse liver 12 [AML12] cells) with RAP1A knockdown or overexpression were used to assess cellular lipid accumulation, fatty acid oxidation, and mechanistic pathways. Mitochondrial function assays, autophagy analysis, and extracellular signal-regulated kinase (ERK) signaling evaluations were conducted, including interventions with an ERK activator and autophagy inhibitor to probe pathway involvement.
Results
LKO mice developed increased adiposity and hepatic steatosis with significantly elevated liver triglycerides, cholesterol, and lipid droplet accumulation, despite unchanged caloric intake. They also exhibited impaired glucose tolerance and insulin resistance, indicating pronounced metabolic dysfunction. RAP1A deficiency led to dysregulated hepatic lipid gene expression—mainly downregulating genes for fatty acid oxidation and lipid catabolism—consistent with exacerbated lipid accumulation. Hepatocytes lacking RAP1A showed similar lipid accumulation, reduced fatty acid oxidation capacity, and altered expression of lipid metabolic enzymes. Mechanistically, RAP1A-deficient livers and cells displayed activated autophagy, particularly mitophagy. RAP1A was found to localize to mitochondrial membranes, and its loss was associated with reduced ERK phosphorylation. Notably, pharmacological activation of the ERK pathway restored ERK phosphorylation and significantly alleviated triglyceride accumulation in RAP1A-knockdown hepatocytes, rescuing the expression of key lipid breakdown enzymes. Conversely, inhibition of excessive autophagy in RAP1A-deficient cells also partially normalized lipid levels. These findings demonstrate that loss of RAP1A triggers hepatic lipid accumulation and metabolic dysregulation through coordinated effects on lipid metabolism genes, mitophagy, and ERK signaling.
Conclusion
RAP1A is a critical regulator of hepatic lipid metabolism, safeguarding against diet-induced steatosis and metabolic dysfunction. Its absence leads to lipid buildup and impaired metabolic homeostasis via disruptions in lipid accumulation, mitochondrial function, autophagy, and ERK signaling.

Others
Dynamic Lipidomic Remodeling and Clinical Correlations after Sleeve Gastrectomy in Obese Subjects: Gakyung Lee, Yeong Chan Lee, Minkuk Park, Seong Min Kim, Ji-Hyeon Park, Dae Ho Lee; Diabetes Metab J. 2026;50(2):396-411. Published online August 14, 2025; DOI: https://doi.org/10.4093/dmj.2025.0120

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Abstract PDF Supplementary Material PubReader ePub

Background
Sleeve gastrectomy (SG) is an effective and the most commonly performed surgical intervention for obesity. However, detailed studies on the underlying mechanisms, particularly those involving lipid metabolism, remain limited. This study aimed to identify novel pathways associated with the metabolic efficacy of SG by assessing alterations in the serum lipidomic profiles of obese subjects following surgery.
Methods
A prospective study of 50 obese participants undergoing laparoscopic SG was conducted at a tertiary medical center. Serum samples were collected before surgery and 6 months after SG. Lipidomic profiling was performed alongside comprehensive follow-up assessments. Statistical analyses explored lipidomic alterations and their correlations with changes in clinical parameters (Clinical trial registration No. KCT0003527 and KCT0009704).
Results
Participants experienced a 25% reduction in body weight 6 months after SG, with a marked reduction (>70%) in hepatic steatosis and insulin resistance, and a 2-fold increase in plasma oxyntomodulin levels. Lipidomic analysis revealed significant molecular shifts in lipid subclasses based on the fatty acyl composition of lipid species, showing a trend toward higher unsaturation and longer carbon chain lengths, as well as metabolic regulation in specific lipid pathways. Key findings included characteristic shifts within triacylglycerols and glycerophospholipids, which were significantly associated with changes in oxyntomodulin levels. Enhanced phosphatidylcholine-to-lysophosphatidylcholine conversion and upregulated ether lipid levels correlated with liver stiffness measures. Metabolic remodeling of sphingolipids—characterized by a decrease in ceramide/sphingomyelin levels and upregulation of the hexosylceramide pathway—emerged as an additional lipidomic signature after SG.
Conclusion
These findings highlight the complex lipidomic remodeling underlying the metabolic efficacy and therapeutic potential of SG.

Citations

Citations to this article as recorded by

Plasma citric and fatty acid alteration linked to optimal weight loss after sleeve gastrectomy in people with morbid obesity
Ji-Hyeon Park, Moongi Ji, Man-Jeong Paik, Seong Min Kim, Dae Ho Lee
Surgery for Obesity and Related Diseases.2026; 22(10): 1163. CrossRef
Hepatic Insulin Resistance and Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: New Insights into Mechanisms and Clinical Implications
Xuan Trong Truong, Dae Ho Lee
Diabetes & Metabolism Journal.2025; 49(5): 964. CrossRef

Reviews

Others
Big Data Research for Diabetes-Related Diseases Using the Korean National Health Information Database: Kyung-Soo Kim, Bongseong Kim, Kyungdo Han; Diabetes Metab J. 2025;49(1):13-21. Published online January 1, 2025; DOI: https://doi.org/10.4093/dmj.2024.0780

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Abstract PDF Supplementary Material PubReader ePub

The Korean National Health Information Database (NHID), which contains nationwide real-world claims data including sociodemographic data, health care utilization data, health screening data, and healthcare provider information, is a powerful resource to test various hypotheses. It is also longitudinal in nature due to the recommended health checkup every 2 years and is appropriate for long-term follow-up study as well as evaluating the relationships between health outcomes and changes in parameters such as lifestyle factors, anthropometric measurements, and laboratory results. However, because these data are not collected for research purposes, precise operational definitions of diseases are required to facilitate big data analysis using the Korean NHID. In this review, we describe the characteristics of the Korean NHID, operational definitions of diseases used for research related to diabetes, and introduce representative research for diabetes-related diseases using the Korean NHID.

Citations

Citations to this article as recorded by

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Metabolic Risk/Epidemiology
Glucagon-Like Peptide-1: New Regulator in Lipid Metabolism: Tong Bu, Ziyan Sun, Yi Pan, Xia Deng, Guoyue Yuan; Diabetes Metab J. 2024;48(3):354-372. Published online April 1, 2024; DOI: https://doi.org/10.4093/dmj.2023.0277

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