Open AccessMetabolic effect of fluvoxamine in mouse peripheral tissues
Author(s) -
Sigal Rozenblit-Susan,
Nava Chapnik,
Oren Froy
Publication year - 2016
Publication title -
molecular and cellular endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.296
H-Index - 144
eISSN - 1872-8057
pISSN - 0303-7207
DOI - 10.1016/j.mce.2016.01.009
Subject(s) - serotonergic , endocrinology , serotonin , medicine , fluvoxamine , serotonin reuptake inhibitor , circadian rhythm , biology , adipose tissue , white adipose tissue , chemistry , receptor , fluoxetine
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.