Diabetes: Chen Yan's team found that lactic acid is involved in regulating obesity-induced insulin resistance

Lactic acid is the end product of glycolysis, a common metabolic intermediate in the body, and is also considered to be a small signaling molecule involved in the regulation of various cellular functions
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Several studies in recent years have also revealed that lactic acid is an important energy carrier in the body, and it is believed that circulating lactic acid is the preferred energy source for metabolism in most organs in the body
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Adipose tissue is responsible for more than 50% of lactic acid production in the body at rest, and lactic acid has also been found to regulate processes such as lipolysis and thermogenesis in adipose tissue
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During obesity, adipose tissue produces higher levels of lactate due to activation of adipose tissue hypoxia signaling
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However, little is known about the function of lactic acid accumulation in adipose tissue during obesity
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Recently, the research group of Chen Yan, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, published a research paper titled: Lactate is a key mediator that links obesity to insulin resistance via modulating cytokine production from adipose tissue in Diabetes, a well-known international journal in the field of diabetes
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Obesity-induced insulin resistance is a major feature of type 2 diabetes, but its mechanism remains to be further elucidated
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This work has deeply studied the lactate metabolism in adipose tissue.
By knocking out or inhibiting the fat lactate transporter MCT1 in mice and cell models, it is found that lactate is an important molecule affecting insulin resistance caused by obesity, suggesting that the regulation of lactate metabolism may be a potential Diabetes therapeutic targets
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Chen Yan's research group studied the monocarboxylic acid transporter MCT1, which is highly expressed in adipocytes, which is the most important lactate transporter in the body
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By constructing mice with adipose tissue-specific knockout of MCT1 and using studies at the cellular level, it was found that MCT1 in adipose tissue mainly mediates the efflux of cellular lactate
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MCT1 knockout mice did not significantly affect body weight in a high-fat diet-induced obesity model, but the mice developed more severe insulin resistance
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Further investigation of this phenotype found that knockout of MCT1 resulted in increased infiltration of pro-inflammatory macrophages in adipose tissue, ultimately leading to severe systemic inflammation in obese mice
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Molecular mechanism studies found that MCT1 knockout increased lactate accumulation in adipocytes, activated adipocyte apoptosis signaling, and affected inflammatory cytokines secreted by adipocytes
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The secreted inflammatory factors recruit macrophages and further amplify inflammatory signals through macrophages, ultimately aggravating systemic insulin resistance
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The effect of lactic acid on obesity-induced insulin resistance This study revealed that lactic acid metabolism in adipose tissue during obesity is a key molecule linking obesity and insulin resistance, providing new ideas for research in this field, suggesting that if the lactic acid metabolism of adipose tissue is interfered with , may prevent diabetes caused by obesity and achieve "fat and healthy"
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Researcher Chen Yan from Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences is the corresponding author of the paper, and doctoral student Lin Yijun is the first author of the paper
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This work was supported by the National Natural Science Foundation of China and the Ministry of Science and Technology, as well as the public technology platform and animal platform of the Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences
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Article link: https://doi.
org/10.
2337/figshare.
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