Metformin decreases meal size and number and increases c-Fos expression in the nucleus tractus solitarius of obese mice
2013
Kim, Hyun-Ju | Zhang, Xian-Hua | Park, Eun Young | Shin, Kyung-Ho | Choi, Sang Hyun | Chun, Boe-Gwun | Kim, Dong-Hoon
Metformin is widely used to treat obese diabetics because of its beneficial effects on body weight, energy intake, and glucose regulation. However, it has not been investigated how oral metformin affects meal patterns, or whether the reduced food intake is associated with neuronal activation in the hindbrain. Accordingly, we investigated how orally administered metformin (150 or 300mg/kg daily for 4 or 7days) reduces body weight in obese mice on a high-fat diet by continuously measuring meal patterns, energy expenditure, and locomotor activity, and whether oral metformin (300mg/kg daily for 3days) increases c-Fos expression in the nucleus tractus solitarius (NTS) and area postrema. Furthermore, we determined whether oral metformin produces a conditioned taste aversion (CTA) in obese mice administered a single dose of metformin (75, 150, or 300mg/kg, p.o.). Metformin (300mg/kg daily for 7days) reduced body weight and adiposity by decreasing nocturnal energy intake but did not significantly change energy expenditure or locomotor activity relative to vehicle, and it transiently decreased nocturnal meal size and reduced meal number throughout the experiments. Furthermore, metformin significantly increased c-Fos immunoreactivity within the NTS of obese mice compared to that in controls and pair-fed group, and induced a CTA at doses of 150 or 300mg/kg. These results indicate that metformin-induced weight loss is associated with a sustained reduction in energy intake maintained by a reduction in meal size and number, and that oral administration of metformin causes visceral illness and neuronal activation in the NTS.
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