White adipocyte dysfunction and obesity-associated pathologies in humans

The prevalence of obesity and associated chronic diseases continues to increase worldwide, negatively impacting on societies and economies. Whereas the association between excess body weight and increased risk for developing a multitude of diseases is well established, the initiating mechanisms by which weight gain impairs our metabolic health remain surprisingly contested. In order to better address the myriad of disease states associated with obesity, it is essential to understand adipose tissue dysfunction and develop strategies for reinforcing adipocyte health. In this Review we outline the diverse physiological functions and pathological roles of human white adipocytes, examining our current knowledge of why white adipocytes are vital for systemic metabolic control, yet poorly adapted to our current obesogenic environment. White adipose tissue serves a plethora of physiological functions, which are compromised in obesity. The mechanisms through which obese white adipose tissue contributes to pathologies including insulin resistance, dyslipidaemia, chronic inflammation, cancer and decreased fertility are emerging. In the future, these insights can be translated into novel drugs for obesity and obesity-associated diseases.