The Effects of Poncirus fructus on Insulin Resistance and the Macrophage-Mediated Inflammatory Response in High Fat Diet-Induced Obese Mice

Abstract

Obesity is a chronic low-grade inflammatory condition in which hypertrophied adipocytes and adipose tissue immune cells, mainly macrophages, contribute to increased circulating levels of proinflammatory cytokines. Obesity-associated chronic low-grade systemic inflammation is considered a focal point and a therapeutic target in insulin resistance and metabolic diseases. We evaluate the effect of Poncirus fructus (PF) on insulin resistance and its mechanism based on inflammatory responses in high-fat diet (HFD)-induced obese mice. Mice were fed an HFD to induce obesity and then administered PF. Body weight, epididymal fat and liver weight, glucose, lipid, insulin, and histologic characteristics were evaluated to determine the effect of PF on insulin resistance by analyzing the proportion of macrophages in epididymal fat and liver and measured inflammatory gene expression. PF administration significantly decreased the fasting and postprandial glucose, fasting insulin, HOMA-IR, total-cholesterol, triglycerides, and low-density lipoprotein cholesterol levels. The epididymal fat tissue and liver showed a significant decrease of fat accumulation in histological analysis. PF significantly reduced the number of adipose tissue macrophages (ATMs), F4/80+ Kupffer cells, and CD68+ Kupffer cells, increased the proportion of M2 phenotype macrophages, and decreased the gene expression of inflammatory cytokines. These results suggest that PF could be used to improve insulin resistance through modulation of macrophage-mediated inflammation and enhance glucose and lipid metabolism.