Adipose Tissue Dysfunction and Impaired Metabolic Health in Human Obesity: A Matter of Oxygen?

The number of studies in the field of adipose tissue biology has increased exponentially over the last decade. This shift in research focus is primarily driven by the tremendous increase in the prevalence of obesity and related chronic diseases, including cardiovascular disease and type 2 diabetesmellitus. Adipose tissue is a fascinating and complex organ, with marked effects on whole-body physiology. Intriguingly, expansion of adipose tissue does not necessarily translate into increased metabolic and cardiovascular disease risk. A proportion of obese individuals seems to be relatively protected against worsening of metabolic health (1), suggesting that adipose tissue dysfunction, rather than the amount of fat mass, may be a key factor in the pathophysiology of obesity-related metabolic and cardiovascular diseases (2–4). It is widely accepted that impairments in adipose tissue lipid metabolism, a decreased adipose tissue blood flow (ATBF) and an increased production of proinflammatory cytokines by hypertrophic adipocytes and infiltrating adaptive and innate immune cells are characteristics of dysfunctional adipose tissue in obesity (2, 5). These impairments not only induce insulin resistance locally in the adipose tissue but also have detrimental effects at the wholebody level, thereby affecting metabolic health. The reason for this is that adipose tissue dysfunction in obesity is accompanied by lipid spillover in the circulation and subsequent lipid accumulation in non-adipose tissues (ectopic fat storage), and may contribute to systemic low-grade inflammation, thereby accelerating the development and progression of obesity-related insulin resistance and chronic metabolic diseases (Figure 1) (2).