Metformin decreases meal size and number and increases c-Fos expression in the nucleus tractus solitarius of obese mice

• Published in: Physiology & behavior 2013-02, Vol.110, p.213-220
• Main Authors: Kim, Hyun-Ju, Zhang, Xian-Hua, Park, Eun-Young, Shin, Kyung-Ho, Choi, Sang-Hyun, Chun, Boe-Gwun, Kim, Dong-Hoon
• Format: Article
• Language: English
• Subjects: Animals; Avoidance Learning - drug effects; Behavioral psychophysiology; Biological and medical sciences; Body Weight - drug effects; Circadian Rhythm - drug effects; Conditioned taste aversion; Diet-induced obesity; Dietary Fats - pharmacology; Eating - drug effects; Energy balance; Energy Intake - drug effects; Energy Metabolism - drug effects; Fundamental and applied biological sciences. Psychology; Genes, fos - drug effects; Hypoglycemic Agents - pharmacology; Immunohistochemistry; Male; Meal pattern; Medical sciences; Metabolic diseases; Metformin; Metformin - pharmacology; Mice; Mice, Inbred C57BL; Motor Activity - drug effects; Neuronal activation; Obesity; Obesity - metabolism; Obesity - psychology; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rhombencephalon - drug effects; Rhombencephalon - metabolism; Solitary Nucleus - drug effects; Solitary Nucleus - metabolism; Taste - drug effects
• ISSN: 0031-9384; 1873-507X
• DOI: 10.1016/j.physbeh.2013.01.011

Abstract 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 300 mg/kg daily for 4 or 7 days) 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 (300 mg/kg daily for 3 days) 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 300 mg/kg, p.o.). Metformin (300 mg/kg daily for 7 days) 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 300 mg/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.