The Effects of Metformin Given into the Brain on Food Intake and a Expressions of Hypothalamic Neurotransmitters in the Rats

Kim, Eun Sook; Kim, Jin Yub; Kim, Sang Wook; Park, Joong Yeol; Lee, Ki Up; Hong, Sung Kwan

Abstract

BACKGROUND: Metformin, a biguanide agent, is an oral hypoglycemic agent frequently prescribed to non-insulin-dependent diabetic patients. In adclition to the glucose lowering effect, it is known to suppress fol intake, but the action mechanism for food intake suppression is not known yet. Hypothalamic neuropeptide Y (NPY) is recently identified that strongly stimulates food intake and melanin concentrating hormone (MCH) is also known to be involved in the ingestion of foods. The effects of mettormin on these substances are not known yet. We tried to define the effect of metformin administered into the lateral ventricle on the amount of food intake and mRNA expressions of NPY and MCH.
METHODS
Each rat was housed in a separate cage, and brain cannula was set into the lateral ventricle and proper position was checked by the response to angiotensin-II injection. Metformin l ug (1 ug/uL) or normal saline (1 uL) were injected daily into the lateral ventricle for 4 days in the Metformin group (n=7) and Control group (n=6) respectively, and the amount of food intake and weight change were recrded. Expressions of corticotropin releasing hormone mRNA in paraventricular nucleus, NPY mRNA in arcuate nucleus, and MCH mRNA in lateral hypothalamus were measured by the in situ hybridization technique.
RESULTS
The amount of food intake was lower in metformin group than that in control group by 14~35% during the study period (p<0.05). Changes of body weight was -18+9 g (mean+SD) in metformin group and -2+11 g in control group. But mRNA expressions of NPY, MCH and CRH were not different between the groups (p>0.05).
CONCLUSION
Metformin injected into the brain reduced the amount of food intake and body weight without the changes of NPY and MCH mRNAs. This study suggests that metformin suppress food intake by directly acting in the brain, but these effects are not through the changes of NPY and MCH mRNA expressions.