Physiological mechanisms of TLR4 in glucolipid metabolism regulation: Potential use in metabolic syndrome prevention

Over-nourishment or an unbalanced diet has been linked to an increase in the prev-alence of metabolic syndrome. An imbalance in glucolipid metabolism is a major cause of meta-bolic syndrome, which has consequences for human health. Toll-like receptor 4 (TLR4), a member of the innate immune pattern recognition receptor family, is involved in inflammation-related disorders, autoimmune diseases, and tumors. Recent research has shown that TLR4 plays a key role in glucolipid metabolism, which is linked to insulin resistance, intes-tinal flora, and the development of chronic inflammation. TLR4 activation regulates glucolipid metabolism and contributes to the dynamic relationship between innate immunity and nutrition-related disorders. Further, TLR4 regulates glucolipid metabolism by controlling glycol-ysis and pyruvate oxidative decarboxylation, interfering with insulin signaling, regulating adipo-genic gene expression levels, influencing preadipocyte differentiation and lipid accumulation, and altering the intestinal microbiota and permeability. TLR4 functions may provide new thera-peutic applications for the prevention and treatment of metabolic syndrome. The purpose of this review is to enrich mechanistic research of diabetes, atherosclerosis, and other nutrition-related disorders by summarizing the role of TLR4 in the regulation of glucolipid metabolism as well as its physiological mechanisms.& COPY; 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Ital-ian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.