Walnut Meal Extracts Rich In Polyphenols Mitigate Insulin Resistance and Modulate Gut Microbiota in High Fat Diet-Fed Rats

Abstract

Walnut kernel is a traditional Chinese herb recorded in the Chinese Pharmacopoeia with the efficacies of invigorating kidney, tonifying lung, and relaxing bowel. However, the potential mechanisms were unclear. This article aims to uncover the interdict mechanisms of walnut meal extracts (WMP) on high-fat diet (HFD) induced metabolic disorders in rats and reveal how the WMP benefits are associated with changes in the intestinal flora. Sprague-Dawley (SD) rats were fed a standard chow diet or an HFD for 18 weeks. After 6 weeks, the HFD rats were supplemented with 750 mg WMP/kg body weight or the vehicle for 12 weeks. The structure of gut microbiota was assessed by analyzing 16S rDNA sequences. WMP suppressed the weight gain and visceral obesity. WMP treatment also improved lipid profiles and increased antioxidative activities. WMP fully reversed hepatic steatosis with the upregulation of adipocytokines involved in lipid catabolism (e.g., adiponectin, PPAR-γ, visfatin, CEBPα) and the increased activities of lipoprotein lipase and hormone-sensitive lipase, which were associated with glucose tolerance improvement and insulin resistance (IR) mitigation. As revealed by 16S rDNA sequencing, WMP restored the diversity of intestinal flora reduced by HFD. WMP dramatically reduced the abundance of Gram-negative bacteria, especially Fusobacterium varium and Bacteroides vulgatus, and sharply increased the abundance of Lactobacillus animalis decreased by HFD. Our findings demonstrated that WMP suppressed the weight gain and adiposity in HFD-fed rats and fully reversed HFD induced IR and hepatic steatosis while dramatically reducing the abundance of Fusobacteriaceae and Enterobacteriaceae, underscoring the gut-liver axis as a primary target of walnut polyphenols.