Nutrients, Physical Activity, and Mitochondrial Dysfunction in the Setting of Metabolic Syndrome

Metabolic syndrome (MetS) is a cluster of metabolic risk factors for diabetes, coronary heart disease, non-alcoholic fatty liver disease, and some tumors. It includes insulin resistance, visceral adiposity, hypertension, and dyslipidemia. MetS is primarily linked to lipotoxicity, with ectopic fat deposition from fat storage exhaustion, more than obesity per se. Excessive intake of long-chain saturated fatty acid and sugar closely relates to lipotoxicity and MetS through several pathways, including toll-like receptor 4 activation, peroxisome proliferator-activated receptor-gamma regulation (PPAR gamma), sphingolipids remodeling, and protein kinase C activation. These mechanisms prompt mitochondrial dysfunction, which plays a key role in disrupting the metabolism of fatty acids and proteins and in developing insulin resistance. By contrast, the intake of monounsaturated, polyunsaturated, and medium-chain saturated (low-dose) fatty acids, as well as plant-based proteins and whey protein, favors an improvement in sphingolipid composition and metabolic profile. Along with dietary modification, regular exercises including aerobic, resistance, or combined training can target sphingolipid metabolism and improve mitochondrial function and MetS components. This review aimed to summarize the main dietary and biochemical aspects related to the physiopathology of MetS and its implications for mitochondrial machinery while discussing the potential role of diet and exercise in counteracting this complex clustering of metabolic dysfunctions.

Automated summary

Metabolic syndrome (MetS) is a cluster of metabolic risk factors associated with various diseases. High intake of long-chain saturated fatty acid and sugar contributes to lipotoxicity and MetS through several pathways. However, intake of monounsaturated, polyunsaturated, and medium-chain saturated fatty acids, as well as plant-based proteins and whey protein, can improve metabolic profile. In addition, regular exercises can target sphingolipid metabolism and improve mitochondrial function and MetS components.