title: Metabolic effect of fluvoxamine in mouse peripheral tissues.
abstract: Serotonin leads to reduced food intake and satiety. Disrupted circadian rhythms lead to hyperphagia and obesity. The serotonergic and circadian systems are intertwined, as the central brain clock receives direct serotonergic innervation and, in turn, makes polysynaptic output back to serotonergic nuclei. Our objective was to test the hypothesis that peripherally serotonin alters circadian rhythms leading to a shift towards fat synthesis and weight gain. We studied the effect of serotonin and fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), on the circadian clock and metabolic gene and protein expression in mouse liver, muscle and white adipose tissue (WAT) and cell culture. We found that serotonin and/or the SSRI fluvoxamine led to fat accumulation in mouse liver and hepatocytes by shifting metabolism towards fatty acid synthesis mainly through low average levels of phosphorylated acetyl CoA carboxylase (pACC) and phosphorylated protein phosphatase 2A (pPP2A). This shift towards fat synthesis was also observed in adipose tissue. Muscle cells were only slightly affected metabolically by serotonin or fluvoxamine. In conclusion, although centrally it leads to increased satiety, in peripheral tissues, such as the liver and WAT, serotonin induces fat accumulation.
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 76100, Israel.
authors.forename: Sigal
authors.initials: S
authors.lastname: Rozenblit-Susan
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 76100, Israel.
authors.forename: Nava
authors.initials: N
authors.lastname: Chapnik
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 76100, Israel. Electronic address: oren.froy@mail.huji.ac.il.
authors.forename: Oren
authors.initials: O
authors.lastname: Froy
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000187:drug effects*; D016666:Fluvoxamine / Q000008:administration & dosage* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000103:Acetyl-CoA Carboxylase; D016666:Fluvoxamine; D054648:Protein Phosphatase 2; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
keywords: ACC; FAS; Fat; Metabolism; PP2A; SSRI; Serotonin