The Beige Adipocyte as a Therapy for Metabolic Diseases

Abstract

Adipose tissue is traditionally categorized into white and brown relating to their function and morphology. 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 more energetically active, with a greater number of mitochondria and energy production in the form of heat. Since adult humans possess significant amounts of active brown fat depots and its 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 themselves from white adipocytes. The presence of brown and beige adipocyte in human adults has acquired attention as a possible therapeutic intervention for metabolic diseases. Importantly, adult human brown appears to be mainly composed of beige-like adipocytes, making this cell type an attractive therapeutic target for obesity and obesity-related diseases, such as atherosclerosis, arterial hypertension and diabetes mellitus type 2. Because many epigenetics changes can affect beige adipocyte differentiation from adipose progenitor cells, the knowledge of the circumstances that affect the development of beige adipocyte cells may be important to new pathways in the treatment of metabolic diseases. New molecules have emerged as possible therapeutic targets, which through the impulse to develop beige adipocytes can be useful for clinical studies. In this review will discuss some recent observations arising from the unique physiological capacity of these cells and their possible role as ways to treat obesity and diabetes mellitus type 2.

Keywords: beige adipose cell; diabetes mellitus 2; metabolic disease; obesity therapy.

Figure 1

Determining factors in differentiation of adipose cell Beige. 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. BMP7 triggers production of mesenchymal adipose cells to brown adipose cells. Both exercise and some hormones can increase the capacity of adipose stem cells 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 the type 2 macrophage. IL-33 has the ability activating the differentiation of adipocytes directly Beige. 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 type 2 macrophage; FGF21: Fibroblastic growth factor 21; PPARγ: Peroxisome proliferator-activated receptor gamma; TR: Thyroid receptors; FXR: Farnesoid X receptor; BNP: Brain natriuretic factor.

Figure 2

The effects of cold on the induction of thermogenic active adipocyte. The secretion of noradrenaline 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. Calsyntenin 3β (CLSTN3β) that is expressed in beige and brown adipocytes aids the secretion of a growth-factor protein, S100b that facilitates the growth of projections from neurons and noradrenaline secretion. FFA: Free fatty acid; M2: Macrophages 2, SNS: Sympatic Nervous System; PKA: Protein Kinase A; UCP1: Uncoupling protein 1; PGC-1α: Peroxisome proliferator-activated receptor-gamma coactivator alpha 1; CLSTN3β: Calsyntenin 3β; S100b, S100 calcium-binding protein b.