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Original Article
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
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  • 27 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

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  • Therapeutic effect of treatment with metformin and/or 4-hydroxychalcone in male Wistar rats with nonalcoholic fatty liver disease
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  • 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
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  • Effect of Metformin on Antipsychotic-Induced Metabolic Dysfunction: The Potential Role of Gut-Brain Axis
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  • Metabolic parameters and functional state of hypothalamic signaling systems in AY/a mice with genetic predisposition to obesity and the effect of metformin
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  • Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older C57BL/6J mice
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    Behavioural Brain Research.2016; 301: 1.     CrossRef
  • Intracerebroventricular Metformin Decreases Body Weight But Has Pro-oxidant Effects and Decreases Survival
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  • Metformin alleviates hepatosteatosis by restoring SIRT1-mediated autophagy induction via an AMP-activated protein kinase-independent pathway
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  • Activation of AMP-activated protein kinase by metformin protects against global cerebral ischemia in male rats: Interference of AMPK/PGC-1α pathway
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