Abstract

BackgroundCoffee can regulate glucose homeostasis but the underlying mechanism is unclear. This study investigated the preventive and therapeutic effects of chlorogenic acid (CGA), a polyphenol that is found in coffee, on obesity and obesity-related metabolic endotoxemia.MethodMale 4-week-old C57BL/6 mice were fed either normal chow or a high-fat diet or 20 weeks and half the mice in each group were gavaged with CGA. Oral glucose tolerance tests (OGTTs) and insulin tolerance tests (ITTs) were performed. Markers of inflammation and intestinal barrier function were assayed. The composition of the gut microbiota was analyzed by 16S rRNA high-throughput pyrosequencing. The role of CGA-altered microbiota in metabolic endotoxemia was verified by fecal microbiota transplantation.ResultsCGA protected against HFD-induced weight gain, decreased the relative weight of subcutaneous and visceral adipose, improved intestinal barrier integrity, and prevented glucose metabolic disorders and endotoxemia (P <0.05). CGA significantly changed the composition of the gut microbiota and increased the abundance of short chain fatty acid (SCFA)-producers (e.g., Dubosiella, Romboutsia, Mucispirillum, and Faecalibaculum) and Akkermansia, which can protect the intestinal barrier. In addition, mice with the CGA-altered microbiota had decreased body weight and fat content and inhibited metabolic endotoxemia.ConclusionCGA-induced changes in the gut microbiota played an important role in the inhibition of metabolic endotoxemia in HFD-fed mice.

Highlights

  • The worldwide incidence of obesity has risen in recent decades together with the rapid economic development of societies and changes in lifestyle and dietary habits

  • These results indicated that chlorogenic acid (CGA) treatment inhibited body weight gain and adipose tissue accumulation in high-fat diets (HFDs)-fed mice without limiting food intake

  • To study the effect of CGA on insulin resistance induced in mice by different dietary patterns, fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) index, Oral Glucose Tolerance Test (OGTT), and Insulin Tolerance Test (ITT) were measured in mice fed normal chow or the HFD with or without CGA

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Summary

Introduction

The worldwide incidence of obesity has risen in recent decades together with the rapid economic development of societies and changes in lifestyle and dietary habits. Obesity results from a long-term positive energy balance, an ongoing. CGA Improves IR and Obesity increased food intake and decreased energy expenditure, and the influence of genetic and environmental factors. Long-term obesity leads to a series of metabolic diseases, such as type 2 diabetes, cardiovascular disease, nonalcoholic fatty liver disease, hypertension, malignant tumors, and others has become a global public health threat [2]. Obesity is characterized by chronic low-grade inflammation. The increase of LPS and release of proinflammatory cytokines results in metabolic endotoxemia, which promotes the development of metabolic syndrome, including impaired insulin signaling and chronic low-grade inflammation. Inhibiting the occurrence of chronic low-grade inflammation would be significant in the management of obesity [5, 6]. This study investigated the preventive and therapeutic effects of chlorogenic acid (CGA), a polyphenol that is found in coffee, on obesity and obesity-related metabolic endotoxemia

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