Brown and beige adipose tissue: a novel therapeutic strategy for obesity and type 2 diabetes mellitus

Abstract

Mammalian adipose tissue can be divided into two major types, namely, white adipose tissue (WAT) and brown adipose tissue (BAT). According to classical view, the main function of WAT is to store excess energy in the form of triglycerides, while BAT is a thermogenic tissue that acts a pivotal part in maintaining the core body temperature. White adipocytes display high plasticity and can transdifferentiate into beige adipocytes which have many similar morphological and functional properties with brown adipocytes under the stimulations of exercise, cold exposure and other factors. This phenomenon is also known as 'browning of WAT'. In addition to transdifferentiation, beige adipocytes can also come from de novo differentiation from tissue-resident progenitors. Activating BAT and inducing browning of WAT can accelerate the intake of glycolipids and reduce the insulin secretion requirement, which may be a new strategy to improve glycolipids metabolism and insulin resistance of obese and type 2 diabetes mellitus (T2DM) patients. This review mainly discusses the significance of brown and beige adipose tissues in the treatment of obesity and T2DM, and focuses on the effect of the browning agent on obesity and T2DM, which provides a brand-new theoretical reference for the prevention and treatment of obesity and T2DM.

Keywords: Brown adipose tissue; beige adipose tissue; browning of white adipose tissue; obesity; type 2 diabetes mellitus; white adipose tissue.

Figure 1.

Comparison of white adipocytes, beige adipocytes and brown adipocytes in location, morphology, UCP1 expression level, mitochondrial density, function and marker genes. In adults, the subcutaneous fat is characterized by classic WAT. The BAT on clavicle consists of white, beige and brown adipocytes, while the classic BAT can be found in the deep neck, armpit and adjacent to skeletal muscle tissue. The fat adjacent to gonads, groin, mesentery and peritoneum of adult mice has the characteristics of classical WAT. The beige adipocytes were found in the groin of mice, while the classical BAT was found in the scapular area. Transcription factor 21 (TCF21), Transducin-like enhancer of split 3 (TLE3), Tumour necrosis factor receptor superfamily, member 9(CD137), T-Box 1 (TBX1), Transmembrane protein 26 (TMEM26), LIM homeobox protein 8 (LHX8), zinc finger protein of the cerebellum 1 (ZIC1)

Figure 2.

Protective effects of beige and brown adipose tissue against obesity and T2DM. The recruitment of beige adipocytes and the increase of BAT amount and/or BAT activity can promote the expression of UCP1 and increase heat production. Overexpression of UCP1 protein will enhance glucose uptake, fatty acid oxidation and lipolysis of both beige and brown adipocytes, which leads to increased insulin sensitivity and reduction in blood glucose, blood lipids and fat mass, thus preventing T2DM. Note: Upward pointing green arrows and downward pointing red arrows indicate ‘increase’ and ‘decrease’, respectively

Figure 3.

Detailed mechanisms of anti-obesity and type 2 diabetes with browning agents such as exercise, cold exposure, and brown fat transplantation. Note: The green arrow (￫) indicates activation or promotion

Figure 4.

Detailed mechanisms of anti-obesity and T2DM with endogenous browning agents (miRNA, BMP, Irisin and IL-6). Note: The green arrow (￫) indicates activation or promotion, and Inverted ‘T’ () indicates inhibition

Figure 5.

Detailed mechanisms of anti-obesity and T2DM with browning agents such as β3 AR agonists, TZDs, GLP-1RAs and Berberine etc. Note: The green arrow (￫) indicates activation or promotion