Adipocyte function and the development of cardiometabolic disease

Obesity is a medical disorder caused by multiple mechanisms of dysregulated energy balance. A major consequence of obesity is an increased risk to develop diabetes, diabetic complications and cardiovascular disease. While a better understanding of the molecular mechanisms linking obesity, insulin resistance and cardiovascular disease is needed, translational research of the human pathology is hampered by the available cellular and rodent model systems. Major barriers are the species-specific differences in energy balance, vascular biology and adipose tissue physiology, especially related to white and brown adipocytes, and adipose tissue browning. In rodents, non-shivering thermogenesis is responsible for a large part of energy expenditure, but humans possess much less thermogenic fat, which means temperature is an important variable in translational research. Mouse models with predisposition to dyslipidaemia housed at thermoneutrality and fed a high-fat diet more closely reflect human physiology. Also, adipocytes play a key role in the endocrine regulation of cardiovascular function. Adipocytes secrete a variety of hormones, lipid mediators and other metabolites that directly influence the local microenvironment as well as distant tissues. This is specifically apparent in perivascular depots, where adipocytes modulate vascular function and inflammation. Altogether, these mechanisms highlight the critical role of adipocytes in the development of cardiometabolic disease.