title: The effect of metformin on neuronal activity in the appetite-regulating brain regions of mice fed a high-fat diet during an anorectic period.
abstract: Metformin reduces body weight by decreasing food intake in humans and animals. However, the brain regions involved in metformin-induced anorexia remain unclear. Therefore, we investigated c-Fos expression (FOS), a marker of neuronal activity, in the appetite-regulating brain regions after oral administration of metformin (PO, 300mg/kg daily for 1 or 3days) or vehicle. The body weight and food intake decreased in mice treated with metformin for 3days (RM group) and mice that had the same amount of food as the RM group (Pair-fed group; PF) compared to the control group. FOS expression levels increased in the paraventricular nucleus, area postrema, and central amygdala of mice administered an acute single dose of metformin (SM group) compared to the control mice. In the nucleus tractus solitarius, the FOS expression levels increased in both the SM and RM groups compared to the control group. The FOS expression levels also increased in the nucleus accumbens of the RM group compared to other groups. The FOS expression levels decreased in the ventromedial hypothalamic nucleus in the PF group, but not the RM group, compared to the control group, suggesting a potential hypothalamic area involvement for metformin-induced anorexia. These results suggest that both the hypothalamic and extra-hypothalamic regions are associated with metformin-induced anorexia, which is dependent on metformin treatment duration.
authors.affiliation: Department of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Bo-Yeong
authors.initials: BY
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Mi-Jeong
authors.initials: MJ
authors.lastname: Oh
authors.affiliation: Department of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung-Ho
authors.initials: KH
authors.lastname: Shin
authors.affiliation: Department of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Department of Pharmacology, Korea University College of Medicine, Seoul, Republic of Korea. Electronic address: LDHKIM@korea.ac.kr.
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000855:Anorexia / Q000188:drug therapy* / Q000209:etiology*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D059305:Diet, High-Fat; D004435:Eating / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013997:Time Factors
chemical_list: D007004:Hypoglycemic Agents; D016760:Proto-Oncogene Proteins c-fos; D008687:Metformin
keywords: Appetite; Brain; Food intake; Metformin; Neuronal activation