Abstract
Background: Accumulating data support the fact that the gut microbiota plays an important role in the progression of obesity and its related metabolic disease. Sex-related differences are an important consideration in the study of gut microbiota. Polyphenols can regulate gut microbiota, thereby improving obesity and its associated complications. There have been no studies conducted on the ability of honokiol (HON, an extract from Chinese herbal medicine) to regulate gut microbiota. The aim of this study was to examine whether HON supplementation would improve obesity by regulating the gut microbiota and its related metabolite levels, and whether there were sex-based differences in high-fat diet-induced obese mice.Methods: C57BL/6 mice (n = 120) were fed a normal chow diet (ND group), high-fat diet (HFD group), or HFD plus HON at 200, 400, and 800 mg/kg BW for 8 weeks. Body weight, adipose tissue weight, adipocyte diameter, insulin resistance, blood lipid and serum inflammatory cytokines, gut microbiota, and its metabolite were examined at the end of the experiment.Results: The HON supplementation reduced body weight, adipose tissue weight, adipocyte diameter, insulin resistance, blood lipid, and serum inflammatory cytokine levels in HFD-fed mice, and this effect was significant in the high-dose group. In addition, HON not only reversed gut disorders in HFD-fed mice, such as by enhanced the abundance of Akkermansia and short-chain fatty acids (SCFAs) producing Bacteroides and reduced Oscillospira, but also improved the SCFAs and endotoxin (LPS) levels, although there were sex-based differences. The correlation between several specific genera and obesity-related indexes was revealed through Spearman's correlation analysis. Moreover, HON may have dose-dependent effects on regulating gut microbiota to alleviate obesity.Conclusions: These findings suggest that HON can prevent diet-induced obesity and its associated diseases by regulating the gut microbiota and improving microbial metabolite levels. Moreover, our findings indicate that sex may be an important factor affecting HON activity.
Highlights
Obesity and related metabolic diseases, which are caused by a high-fat diet (HFD) and sedentary lifestyle, have been increasing with the improvements in standard of living and the changing lifestyle and have become an urgent public health problem [1]
Total food intake did not vary significantly among the HFD-fed groups of female mice and male mice except for the H800 group (Figure 1D), where a significant decrease of food efficiency ratio (FER) was observed for the H800 group of female mice and H800 and H200 groups of male mice compared with the HFD group (P < 0.05, Figure 1E), suggesting that the effects of HON on body weight did not result from the reduction of food intake but from the FER
These results imply that HON reduced weight gain in HFD-fed mice and that there were sex-based differences in the body weight, weight gain, and FER (P < 0.05, Figures 1C–E); the food intake of HFD + 800 mg/kg HON male mice was notably lower than that of the female mice (P < 0.05, Figure 1D)
Summary
Obesity and related metabolic diseases, which are caused by a high-fat diet (HFD) and sedentary lifestyle, have been increasing with the improvements in standard of living and the changing lifestyle and have become an urgent public health problem [1]. Studies have demonstrated that Akkermansia can improve the body’s inflammatory response and protect the intestinal barrier [11], Oscillospira is closely related to the body’s inflammatory response and intestinal permeability [13], and Bacteroides can promote health by producing short-chain fatty acids (SCFAs) to provide energy for intestinal epithelial cells and inhibit LPS-induced inflammation [12, 16]. These results suggest that regulating gut microbiota may be an important measure to prevent obesity and obesity-related metabolic syndrome. The aim of this study was to examine whether HON supplementation would improve obesity by regulating the gut microbiota and its related metabolite levels, and whether there were sex-based differences in high-fat diet-induced obese mice
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