Metabolic effect of fluvoxamine in mouse peripheral tissues

Molecular and Cellular Endocrinology
Sigal Rozenblit-SusanOren Froy

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...Continue Reading

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Citations

Oct 31, 2017·International Journal of Obesity : Journal of the International Association for the Study of Obesity·S Rozenblit-SusanO Froy
Jul 20, 2019·American Journal of Physiology. Endocrinology and Metabolism·Elaine M RichardsMaureen Keller-Wood
Oct 28, 2019·Pharmacogenetics and Genomics·Henrik Thyge Corfitsen, Antonio Drago
Jun 10, 2018·Diabetes & Metabolism Journal·Jun NamkungHail Kim
Jan 6, 2021·Archives of Toxicology·Nevena Todorović VukotićSnežana B Pajović
Jun 12, 2018·European Journal of Pharmacology·Manuella da L D BarrosLigia Galindo

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