Abstract
Gut microbiota dysbiosis has a significant role in the pathogenesis of metabolic diseases, including obesity. Nuciferine (NUC) is a main bioactive component in the lotus leaf that has been used as food in China since ancient times. Here, we examined whether the anti-obesity effects of NUC are related to modulations in the gut microbiota. Using an obese rat model fed a HFD for 8 weeks, we show that NUC supplementation of HFD rats prevents weight gain, reduces fat accumulation, and ameliorates lipid metabolic disorders. Furthermore, 16S rRNA gene sequencing of the fecal microbiota suggested that NUC changed the diversity and composition of the gut microbiota in HFD-fed rats. In particular, NUC decreased the ratio of the phyla Firmicutes/Bacteroidetes, the relative abundance of the LPS-producing genus Desulfovibrio and bacteria involved in lipid metabolism, whereas it increased the relative abundance of SCFA-producing bacteria in HFD-fed rats. Predicted functional analysis of microbial communities showed that NUC modified genes involved in LPS biosynthesis and lipid metabolism. In addition, serum metabolomics analysis revealed that NUC effectively improved HFD-induced disorders of endogenous metabolism, especially lipid metabolism. Notably, NUC promoted SCFA production and enhanced intestinal integrity, leading to lower blood endotoxemia to reduce inflammation in HFD-fed rats. Together, the anti-obesity effects of NUC may be related to modulations in the composition and potential function of gut microbiota, improvement in intestinal barrier integrity and prevention of chronic low-grade inflammation. This research may provide support for the application of NUC in the prevention and treatment of obesity.
Highlights
Obesity is a global epidemic associated with poor quality of life and reduced average life expectancy[1]
high-fat diet (HFD) feeding for this period led to significant increases in body and liver weight, epididymal and perirenal fat accumulation, and lipid deposition in adipocytes compared with the ND group (Fig. 1b–f, i, j)
We found that NUC supplementation can prevent dietary-induced obesity, improve lipid metabolic disorders and reduce inflammation, and the potential mechanisms could be due to modulating the composition and potential function of the gut microbiota, promoting Short-chain fatty acid (SCFA) production, and enhancing intestinal barrier integrity
Summary
Obesity is a global epidemic associated with poor quality of life and reduced average life expectancy[1]. The characteristics of obesity include excess fat accumulation in the adipose tissue and organs in the body, a significant increase in plasma lipid levels, and chronic, low-grade inflammation. Excessive body weight increases the risk of many chronic diseases, type 2 diabetes, cardiovascular disease, fatty liver disease, and certain types of cancer[2]. In 2015, a total of 107.7 million children and 603.7 million adults were obese. Since 1980, the prevalence of obesity has doubled in more than 70 countries and has continuously increased in most other countries[3]. Available anti-obesity drugs are of limited efficacy and are associated with serious adverse effects[4]
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