Lactiplantibacillusplantarum ATG-K2 Exerts an Anti-Obesity Effect in High-Fat Diet-Induced Obese Mice by Modulating the Gut Microbiome.

Young-Sil Lee,Jihee Kang,Hae-Jeung Lee,Eun-Jung Park,Daeyoung Lee,Gun-Seok Park,Juyi Park,You-Kyung Lee,Jong-Yeon Kim,Seung-Hyun Ko

doi:10.3390/ijms222312665

Abstract

Obesity is a major health problem. Compelling evidence supports the beneficial effects of probiotics on obesity. However, the anti-obesity effect of probiotics remains unknown. In this study, we investigated the anti-obesity effects and potential mechanisms of Lactiplantibacillus plantarum ATG-K2 using 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese mice. 3T3-L1 cells were incubated to determine the effect of lipid accumulation with lysate of L. plantarum ATG-K2. Mice were fed a normal fat diet or HFD with L. plantarum ATG-K2 and Orlistat for 8 weeks. L. plantarum ATG-K2 inhibited lipid accumulation in 3T3-L1 adipocytes, and reduced body weight gain, WAT weight, and adipocyte size in HFD-induced obese mice, concurrently with the downregulation of PPARγ, SREBP1c, and FAS and upregulation of PPARα, CTP1, UCP1, Prdm16, and ND5. Moreover, L. plantarum ATG-K2 decreased TG, T-CHO, leptin, and TNF-α levels in the serum, with corresponding gene expression levels in the intestine. L. plantarum ATG-K2 modulated the gut microbiome by increasing the abundance of the Lactobacillaceae family, which increased SCFA levels and branched SCFAs in the feces. L. plantarum ATG-K2 exhibited an anti-obesity effect and anti-hyperlipidemic effect in 3T3-L1 adipocytes and HFD-induced obese mice by alleviating the inflammatory response and regulating lipid metabolism, which may be influenced by modulation of the gut microbiome and its metabolites. Therefore, L. plantarum ATG-K2 can be a preventive and therapeutic agent for obesity.

Highlights

Obesity is an extensive public health problem, and its prevalence has been increasing over the last few decades [1]
These results suggest that L. plantarum ATG-K2 has an anti-obesity effect associated with reduced White Adipose Tissue (WAT) weight, independent of food intake
DGAT1 in 3T3-L1 adipocytes and the WAT of high-fat diet (HFD)-induced obese mice. It increased AMPK phosphorylation in 3T3-L1 adipocytes, and mRNA expression levels of fatty acid oxidation and adipocyte browning-related genes, PPARα, CTP1, UCP1, Prdm16, and ND5, which correspond to the inhibition of fat expansion in adipocytes and adipose tissue. These results suggest that L. plantarum ATG-K2 may regulate lipid metabolism by decreasing adipogenesis and lipogenesis and increasing fatty acid oxidation, with enhanced adipocyte browning in WAT, leading to reduced adiposity and anti-obesity effects

Summary

Introduction

Obesity is an extensive public health problem, and its prevalence has been increasing over the last few decades [1]. It has been known as a risk factor for chronic metabolic syndromes, such as hyperlipidemia, type 2 diabetes, and cardiovascular disease; obesity management is important to prevent obesity related complications [1]. A dietary intervention including energy restriction, macronutrients, food, and dietary intake patterns, is recommended for the treatment of obesity. Despite their effectiveness, with a dietary intervention there remains unachieved weight loss [2]. A new approach is needed to prevent and treat obesity with high safety and effectiveness, and bioactive substances, such as polyphenols, antioxidants, prebiotics (dietary fibers), and probiotics are being investigated to prevent and treat obesity

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