Fluoxetine ameliorates high-fat diet-induced metabolic abnormalities partially via reduced adipose triglyceride lipase-mediated adipocyte lipolysis

• Published in: Biomedicine & pharmacotherapy 2021-09, Vol.141, p.111848-111848, Article 111848
• Main Authors: Chiu, Yen-Ju, Tu, Ho-Hsiang, Kung, Mei-Lang, Wu, Hung-Ju, Chen, Yun-Wen
• Format: Article
• Language: English
• Subjects: Adipocytes - drug effects; Adipocytes - metabolism; Adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - enzymology; Adipose Tissue, White - drug effects; Adipose Tissue, White - metabolism; Animals; Antidepressant; Behavior, Animal - drug effects; Depression - complications; Depression - psychology; Diabetes; Diet, High-Fat - adverse effects; Fluoxetine - therapeutic use; Glucose - metabolism; Glucose Tolerance Test; Injections, Intraperitoneal; Lipase - metabolism; Lipolysis - drug effects; Male; Metabolic Diseases - drug therapy; Metabolic Diseases - etiology; Metabolic Diseases - psychology; Mice; Mice, Inbred C57BL; Obesity; PPAR gamma - metabolism; Selective serotonin reuptake inhibitor; Serotonin Uptake Inhibitors - therapeutic use
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2021.111848

Patients with type 2 diabetes mellitus have more risk to develop depression. Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI), is drug for mood and anxiety disorders. Previous studies showed that FLX could induce weight loss in non-depressed clinically overweight individuals. Although the anti-appetite effect of FLX is well-documented, its potential effects on metabolic abnormalities have not been investigated. In this study, we want to investigate whether FLX could be a therapeutic drug against high fat diet (HFD)-induced metabolic disorder. We generated metabolic disorders and depressed mouse model by feeding HFD for 12 weeks at the age of 8 weeks. Then, mice were intraperitoneally injected once daily with FLX (10 mg/kg or 20 mg/kg) for four weeks. Our results showed that FLX alleviated the HFD-induced metabolic dysfunctions and depressive phenotypes in mice. FLX improved systemic glucose homeostasis, at least in part, by improving visceral white adipose tissue (vWAT) insulin signaling. Moreover, FLX reduced circulating plasma leptin level, and decreased the expression of adipose triglyceride lipase (ATGL) and peroxisome proliferator-activated receptor gamma (PPARγ) in vWAT. Our data revealed that FLX also reduced the triglyceride (TG) accumulation in vWAT. Therefore, these findings suggest that FLX exhibits significant potential on comorbidity of metabolic disorder and depression in mice. •Fluoxetine alleviated high-fat diet (HDF)-induced metabolic disorder in mice.•Fluoxetine reduced the HFD-induced upregulation of leptin levels.•Fluoxetine improved visceral white adipose tissue (vWAT) insulin signaling.•Fluoxetine reduced adipose triglyceride lipase (ATGL) expression in vWAT.