Piperine protects against pancreatic β-cell dysfunction by alleviating macrophage inflammation in obese mice

• Published in: Life sciences (1973) 2021-06, Vol.274, p.119312-119312, Article 119312
• Main Authors: Yuan, Yanting, Zhou, Ji, Hu, Ruixin, Zou, Linhai, Ji, Lixia, Jiang, Guohui
• Format: Article
• Language: English
• Subjects: Accumulation; Adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - immunology; Adipose Tissue - pathology; Alkaloids - pharmacology; Animals; Benzodioxoles - pharmacology; Beta cells; Biomarkers; Blood glucose; CD11c antigen; Cholesterol; Cytochrome P-450 Enzyme Inhibitors - pharmacology; Cytokines; Dedifferentiation; Diabetes mellitus; Galectin-3; Glucose; Glucose tolerance; High fat diet; Hyperinsulinemia; IL-1β; Immunofluorescence; Inflammation; Inflammation - drug therapy; Inflammation - etiology; Inflammation - pathology; Insulin; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - immunology; Insulin-Secreting Cells - pathology; Interleukins; Islet inflammation; Lipopolysaccharides; Macrophage; Macrophage Activation - drug effects; Macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - pathology; Male; Metabolism; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Obesity - complications; Pancreas; Piperidines - pharmacology; Piperine; Polarization; Polymerase chain reaction; Polyunsaturated Alkamides - pharmacology; Rosiglitazone; Serum levels; TOR protein; Triglycerides; β-cell dysfunction
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2021.119312

Piperine, the major pharmacological ingredient of pepper, can delay the procession of “obesity to diabetes”. However, the underlying mechanism remains unclear. This study aims to investigate whether piperine protects against β-cell dysfunction by inhibiting macrophage accumulation and M1-like polarization. Pre-diabetic model was induced by feeding 60% high-fat diet (HFD) in C57BL/6C mice, piperine (15 or 30 mg/kg/day) and rosiglitazone (4 mg/kg/day) were given orally for 8 weeks. Oral glucose tolerance test (OGTT), insulin tolerance test (ITT), fasting blood glucose (FBG), total cholesterol (TC) and triglyceride (TG) were used to assay the disorder of glycolipid metabolism. Serum levels of cytokines and insulin were measured by Elisa. Hyperglycemic clamp assay was carried out to evaluate β-cell function. RT-PCR, immunofluorescence and western blot were used to detect the expression of biomarkers associated with macrophage polarization and β-cell dedifferentiation. Piperine protected against β-cell dysfunction, indicated by the improvement of hyperinsulinemia, OGTT and increased glucose infusion rate (GIR). Piperine dramatically reduced the serum levels of lipopolysaccharide (LPS), interleukin-1β (IL-1β) and Galectin-3 (Gal-3), suppressed the expression of M1-like cytokines (CD11c, IL-1β and Gal-3) in epididymal adipose tissues and islets. Furthermore, piperine partially reversed the down-regulation of Pdx1, inhibited the up-regulation of ALDH1A3 in β-cell, and these effects were closely related to the mTOR/S6/4E-BP1 signal pathway. Piperine markedly ameliorates the dedifferentiation and dysfunction of β-cell by inhibiting the accumulation and M1-like polarization of macrophages in visceral adipose tissues and islets.