Dietary lactic acid ameliorates high-fat diet-induced obesity by promoting lactate transport and activating GPR81-mediated thermogenesis

Abstract

Obesity and its associated metabolic diseases pose a severe threat to human health, necessitating the identification of safe and effective nutritional intervention mechanisms. Lactic acid, a key flavor and functional component in fermented foods such as yogurt, sauerkraut, and fermented meat products, is widely present in the daily diet. Beyond contributing to the characteristic sour taste and preservative effects of these foods, recent studies have demonstrated that lactate serves as an energy substrate and signaling molecule in the body, playing an crucial role in metabolic regulation. However, its underlying mechanisms remain unclear. This study aims to investigate the mechanisms by which dietary lactic acid helps alleviate obesity. Using a high-fat diet-induced obesity mouse model, the effects of lactic acid on body weight, glucose tolerance, insulin sensitivity, and lipid metabolism were examined. The results demonstrated that exogenous lactic acid intervention effectively reduced the body weight of high-fat diet-induced obese mice, while improving glucose tolerance and insulin sensitivity. Lactic acid gavage significantly increased the accumulation of lactate in tissues and improved liver lipid deposition by activating the lactate transporters monocarboxylate transporter 1(MCT1) and monocarboxylate transporter 4(MCT4), as well as the lactate-specific receptor G-protein-coupled receptor 81(GPR81). These effects enhanced lipid metabolism and thermogenesis in adipose tissue, thus alleviating obesity and its metabolic syndrome. This study provides new theoretical evidence for dietary lactic acid as an intervention strategy for obesity.

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