Skeletal muscles and gut microbiota-derived metabolites: novel modulators of adipocyte thermogenesis

Abstract

Obesity occurs when overall energy intake surpasses energy expenditure. White adipose tissue is an energy storage site, whereas brown and beige adipose tissues catabolize stored energy to generate heat, which protects against obesity and obesity-associated metabolic disorders. Metabolites are substrates in metabolic reactions that act as signaling molecules, mediating communication between metabolic sites (i.e., adipose tissue, skeletal muscle, and gut microbiota). Although the effects of metabolites from peripheral organs on adipose tissue have been extensively studied, their role in regulating adipocyte thermogenesis requires further investigation. Skeletal muscles and intestinal microorganisms are important metabolic sites in the body, and their metabolites play an important role in obesity. In this review, we consolidated the latest research on skeletal muscles and gut microbiota-derived metabolites that potentially promote adipocyte thermogenesis. Skeletal muscles can release lactate, kynurenic acid, inosine, and β-aminoisobutyric acid, whereas the gut secretes bile acids, butyrate, succinate, cinnabarinic acid, urolithin A, and asparagine. These metabolites function as signaling molecules by interacting with membrane receptors or controlling intracellular enzyme activity. The mechanisms underlying the reciprocal exchange of metabolites between the adipose tissue and other metabolic organs will be a focal point in future studies on obesity. Furthermore, understanding how metabolites regulate adipocyte thermogenesis will provide a basis for establishing new therapeutic targets for obesity.

Comprehensive analysis of key host gene-microbe networks in the cecum tissues of the obese rabbits induced by a high-fat diet

“…Clostridium butyricum CCFM1299 could reduce obesity by increasing energy expenditure and regulating host bile acid metabolism (Liao et al, 2023). Simultaneously, studies confirmed that bile acids, butyric acid, succinate, cinnabarinic acid, urolithin A, and asparagine produced by gut microbiota were involved in regulating metabolic pathways in adipose tissue cells, such as PKA, PPAR-alpha, PGC-1a, and mTORC1 signaling pathways (Thibaut and Bindels, 2022;Tang et al, 2023). However, the circulatory metabolic system and cooperative mechanism among gut microbiota, gut metabolites, and host genes in the pathogenesis of diet-induced obesity have not been fully understood yet.…”

CO2-Breathing Prior to Simulated Diving Increases Decompression Sickness Risk in a Mouse Model: The Microbiota Trail Is Not Forgotten

“…Recent work suggests that the microbiota plays an increasingly important role in thermoregulation through its metabolic derivatives [38] or through its serotonergic effects via modulation of the gut-brain axis [32,33]. For instance, the inhibition of serotonin reuptake with fluoxetine has been shown to reduce DCS [27,28] and it would be interesting to explore this question further through the influence of the microbiota.…”

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“…Clostridium butyricum CCFM1299 could reduce obesity by increasing energy expenditure and regulating host bile acid metabolism (Liao et al, 2023). Simultaneously, studies confirmed that bile acids, butyric acid, succinate, cinnabarinic acid, urolithin A, and asparagine produced by gut microbiota were involved in regulating metabolic pathways in adipose tissue cells, such as PKA, PPAR-alpha, PGC-1a, and mTORC1 signaling pathways (Thibaut and Bindels, 2022;Tang et al, 2023). However, the circulatory metabolic system and cooperative mechanism among gut microbiota, gut metabolites, and host genes in the pathogenesis of diet-induced obesity have not been fully understood yet.…”