Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome

Abstract

Over the past decade, great progress has been made in understanding the complexity of adipose tissue biology and its role in metabolism. This includes new insights into the multiple layers of adipose tissue heterogeneity, not only differences between white and brown adipocytes, but also differences in white adipose tissue at the depot level and even heterogeneity of white adipocytes within a single depot. These inter- and intra-depot differences in adipocytes are developmentally programmed and contribute to the wide range of effects observed in disorders with fat excess (overweight/obesity) or fat loss (lipodystrophy). Recent studies also highlight the underappreciated dynamic nature of adipose tissue, including potential to undergo rapid turnover and dedifferentiation and as a source of stem cells. Finally, we explore the rapidly expanding field of adipose tissue as an endocrine organ, and how adipose tissue communicates with other tissues to regulate systemic metabolism both centrally and peripherally through secretion of adipocyte-derived peptide hormones, inflammatory mediators, signaling lipids, and miRNAs packaged in exosomes. Together these attributes and complexities create a robust, multidimensional signaling network that is central to metabolic homeostasis.

Figure 1. Heterogeneity of adipose tissue at multiple levels.

(A) Human adipose tissue illustrating the multiple depots of brown and white subcutaneous and visceral fat. The different roles, properties, and marker/development genes of these depots are indicated. (B) Heterogeneity of adipose tissue in the mouse, showing different depots of white adipose tissue, each containing a mixture of white adipocytes of different subtypes.

Figure 2. Adipose tissue development and remodeling in health and disease.

From left to right, the figure illustrates the conversion of preadipocytes to mature adipocytes followed by adipose expansion due to preadipocyte proliferation and hyperplasia of adipocytes followed by adipocyte hypertrophy, adipose tissue inflammation, and changes in adipocyte hormone leading to insulin resistance. In lipodystrophy this process is also disrupted, leading to insulin resistance.

Figure 3. Adipocyte hormones in intertissue communication.

The figure illustrates different classes of adipocyte hormones and their varied effects on metabolism and the development of insulin sensitivity or resistance. BCAA, branched-chain amino acids; GDF, growth differentiation factor ; Nrg4, neuroregulin 4.