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Diet and Obesity-Induced Methylglyoxal Production and Links to Metabolic Disease

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CHEMICAL RESEARCH IN TOXICOLOGY
卷 34, 期 12, 页码 2424-2440

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AMER CHEMICAL SOC
DOI: 10.1021/acs.chemrestox.1c00221

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  1. NIDDK [R21DK12785]

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The obesity rate in the United States has reached 42.4% and has become a national epidemic. Obesity is a complex condition influenced by various factors, with a Western diet high in processed foods, red meat, and sugar being associated with elevated rates of obesity. Obesity increases the risk of multiple pathologies and is linked to the production of MG through altered metabolic pathways, which in turn impact cellular function.
The obesity rate in the United States is 42.4% and has become a national epidemic. Obesity is a complex condition that is influenced by socioeconomic status, ethnicity, genetics, age, and diet. Increased consumption of a Western diet, one that is high in processed foods, red meat, and sugar content, is associated with elevated obesity rates. Factors that increase obesity risk, such as socioeconomic status, also increase consumption of a Western diet because of a limited access to healthier options and greater affordability of processed foods. Obesity is a public health threat because it increases the risk of several pathologies, including atherosclerosis, diabetes, and cancer. The molecular mechanisms linking obesity to disease onset and progression are not well understood, but a proposed mechanism is physiological changes caused by altered lipid peroxidation, glycolysis, and protein metabolism. These metabolic pathways give rise to reactive molecules such as the abundant electrophile methylglyoxal (MG), which covalently modifies nucleic acids and proteins. MG-adducts are associated with obesity-linked pathologies and may have potential for biomonitoring to determine the risk of disease onset and progression. MG-adducts may also play a role in disease progression because they are mutagenic and directly impact protein stability and function. In this review, we discuss how obesity drives metabolic alterations, how these alterations lead to MG production, the association of MG-adducts with disease, and the potential impact of MG-adducts on cellular function.

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