Biology of Beige Adipocyte and Possible Therapy for Type 2 Diabetes and Obesity

Abstract

All mammals own two main forms of fat. The classical white adipose tissue builds up energy in the form of triglycerides and is useful for preventing fatigue during periods of low caloric intake and the brown adipose tissue instead of inducing fat accumulation can produce energy as heat. Since adult humans possess significant amounts of active brown fat depots and their mass inversely correlates with adiposity, brown fat might play an important role in human obesity and energy homeostasis. New evidence suggests two types of thermogenic adipocytes with distinct developmental and anatomical features: classical brown adipocytes and beige adipocytes. Beige adipocyte has recently attracted special interest because of its ability to dissipate energy and the possible ability to differentiate itself from white adipocytes. Importantly, adult human brown adipocyte appears to be mainly composed of beige-like adipocytes, making this cell type an attractive therapeutic target for obesity and obesity-related diseases. Because many epigenetic changes can affect beige adipocyte differentiation, the knowledge of the circumstances that affect the development of beige adipocyte cells may be important for therapeutic strategies. In this review we discuss some recent observations arising from the great physiological capacity of these cells and their possible role as ways to treat obesity and diabetes mellitus type 2.

Figure 1

The effects of cold on the induction of thermogenic active adipocyte. The secretion of norepinephrine (NE) directly from nervous sympathetic system or indirectly through catecholamine secretion by macrophage type 2 can stimulate glucose uptake in fat cells and improve the regulation of carbohydrate. Both glucose and triglycerides are used by UCP1 protein to increase thermogenesis. FFA: free fatty acid; M2: macrophages 2, SNS: sympathetic nervous system; PKA: protein kinase A; UCP1: uncoupling protein 1; PGC-1α: peroxisome proliferator-activated receptor-gamma coactivator alpha 1.

Figure 2

Determining factors in differentiation of beige adipose cell. The adipose mesenchymal cells can be influenced by the retinoblastoma protein (pRb) and take decision to differentiate into fat cells when pRb is blocked. The EID1 protein among others can determine the differentiation of beige cells adipocytes from mesenchymal stem cells (see [11]). BMP7 triggers production of mesenchymal adipose cells to brown adipose cells. Both exercise and some hormones can increase the capacity of adipose stem cells to differentiate into beige adipocytes. Recently, it has been observed that cells of the innate immune system type 2 can secrete interleukins stimulating the production of IL-4 by eosinophils and norepinephrine production through macrophage type 2. IL-33 has the ability to activate the differentiation of beige adipocytes directly. ADMSC: adipose mesenchymal stem cell; PC1: Prohormone Convertase 1; ILC-2: group 2 innate lymphoid cells; BMP7: bone morphogenic protein 7; EID1: EP300-interacting inhibitor of differentiation 1; M2 ATM: adipose tissue macrophage 2; FGF21: fibroblastic growth factor 21; PPARg: peroxisome proliferator-activated receptor gamma; TR: thyroid receptors; FXR: farnesoid X receptor; BNP: brain natriuretic factor.