Journal of internal medicine
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Obesity prevalence continues to rise worldwide, posing a substantial burden on people's health. However, up to 45% of obese individuals do not suffer from cardiometabolic complications, also called the metabolically healthy obese (MHO). Concurrently, up to 30% of normal-weight individuals demonstrate cardiometabolic risk factors that are generally observed in obese individuals, the metabolically obese normal weight (MONW). ⋯ For some, this association was mediated through favourable effects on body fat distribution. Other studies that characterized the genetic susceptibility of insulin resistance found that a higher susceptibility was associated with lower overall adiposity due to less fat accumulation at hips and legs, suggesting that an impaired capacity to store fat subcutaneously or a preferential storage in the intra-abdominal cavity may be metabolically harmful. Clearly, more work remains to be done in this field, first through gene discovery and subsequently through functional follow-up of identified genes.
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Environmental and socioeconomic changes over the past thirty years have contributed to a dramatic rise in the worldwide prevalence of obesity. Heart disease is amongst the most serious health risks of obesity, with increases in both atherosclerotic coronary heart disease and heart failure among obese individuals. In this review, we focus on primary myocardial alterations in obesity that include hypertrophic remodelling and diastolic dysfunction. ⋯ Lipotoxicity has been modelled in mice using high-fat diet feeding, inbred lines with mutations in leptin receptor signalling, and in genetically engineered mice with enhanced myocardial fatty acid uptake, altered lipid droplet homoeostasis or decreased cardiac fatty acid oxidation. These studies, along with findings in cell culture model systems, indicate that the molecular pathophysiology of lipid overload involves endoplasmic reticulum stress, alterations in autophagy, de novo ceramide synthesis, oxidative stress, inflammation and changes in gene expression. We highlight recent advances that extend our understanding of the impact of obesity and altered lipid metabolism on cardiac function.