Abstract

Adipose tissue is a critical endocrine and immunological organ that regulates systemic energy homeostasis. During the pathogenesis of obesity, adipocyte hypertrophy is accompanied by adipose tissue inflammation, impeding insulin sensitivity and endocrine function of adipose tissue and other tissues. Adipocyte cholesterol accumulates in proportion to triglyceride as adipocytes undergo hypertrophy. Recent studies suggest that dietary cholesterol contributes to increased adipocyte cholesterol. However, how dietary cholesterol accumulates in adipocytes and its metabolic consequences are poorly understood. This review summarizes recent advances in knowledge of adipocyte cholesterol balance and highlights the emerging role of dietary cholesterol in adipose tissue cholesterol balance, inflammation, and systemic energy metabolism. Perturbation of cholesterol balance in adipocytes alters intracellular cholesterol distribution and modulates adipocyte insulin and proinflammatory signaling. Adipocyte cholesterol levels are maintained by a balance between dietary cholesterol uptake from triglyceride-enriched lipoproteins and cellular cholesterol efflux to HDL. Recent animal studies established a critical role for dietary cholesterol in promoting adipose tissue inflammation, thereby worsening obesity-mediated metabolic complications. Recent studies identified high dietary cholesterol as a potentiator of adipose tissue inflammation and dysfunction. Reducing excessive dietary cholesterol intake is suggested as a simple, but novel, way to attenuate obesity-associated metabolic diseases.

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