Metabolic effect of fluvoxamine in mouse peripheral tissues. (15th March 2016)

• Record Type: Journal Article
• Authors: Rozenblit-Susan, Sigal; Chapnik, Nava; Froy, Oren
• Is Part Of: Molecular and cellular endocrinology. Volume 424(2016)
• Page Start: 12
• Page End: 22
• Publication Date: 2016-03-15
• Subjects: Serotonin -- SSRI -- Metabolism -- Fat -- ACC -- FAS -- PP2A; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2016.01.009
• Languages: English
• ISSNs: 0303-7207

Abstract

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. Highlights: Serotonin and/or fluvoxamine lead to fat accumulation in liver. Serotonin and/or fluvoxamine lead to fat accumulation in adipose tissue. Muscle cells are only slightly affected metabolically by serotonin or fluvoxamine. Fluvoxamine leads to a phase advance in circadian oscillation in muscle.