Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

Abstract

The ongoing obesity pandemic generates a constant need to develop new therapeutic strategies to restore the energy balance. Therefore, the concept of activating brown adipose tissue (BAT) in order to increase energy expenditure has been revived. In mammals, two developmentally distinct types of brown adipocytes exist; the classical or constitutive BAT that arises during embryogenesis, and the beige adipose tissue that is recruited postnatally within white adipose tissue (WAT) in the process called browning. Research of recent years has significantly increased our understanding of the mechanisms involved in BAT activation and WAT browning. They also allowed for the identification of critical molecules and critical steps of both processes and, therefore, many new therapeutic targets. Several non-pharmacological approaches, as well as chemical compounds aiming at the induction of WAT browning and BAT activation, have been tested in vitro as well as in animal models of genetically determined and/or diet-induced obesity. The therapeutic potential of some of these strategies has also been tested in humans. In this review, we summarize present concepts regarding potential therapeutic targets in the process of BAT activation and WAT browning and available strategies aiming at them.

Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to Thermogenesis

“…Mitochondria is rich in BAT, and the physiological function of it is recognized by non-trembling heat, moreover, mitochondrial biogenesis plays a crucial role in generating heat in brown fat ( 41 ). This in turn is regarded beneficial to improve obesity by activating brown fat to increase energy expenditure and white fat browning ( 42 ). Researchers have found that hypothalamus can stimulate eating and influence the expression of UCP-1 mRNA ( 43 , 44 ).…”

Tyrosol May Prevent Obesity by Inhibiting Adipogenesis in 3T3-L1 Preadipocytes

“…According to AMPK activation, HSL phosphorylation increased following TR 500 μ M administration ( p < 0.001) ( Figure 5(c) ). Intriguingly, the activatory phosphorylation of AMPK (Thr172) following TR treatment and the subsequent increase in ATGL-mediated lipolysis promote uncoupling protein 1 (UCP1) expression leading to the initial step of adipose tissue browning [ 36 ]. Accordingly, both TR 300 and 500 μ M enhanced the expression levels of UCP1 in fully differentiated 3T3-L1 ( p < 0.05 and p < 0.001, respectively) ( Figure 5(d) ), suggesting that TR administration may reduce adipogenesis by promoting adipose tissue browning.…”

SGLT2 Inhibitor-Induced Sympathoexcitation in White Adipose Tissue: A Novel Mechanism for Beiging

“…There is now evidence for a third type of adipose tissue, beige adipose tissue, which has been found in WAT depots but is more energetically active like BAT [ 3 ]. The induction of beige adipocyte biogenesis or beiging in WAT depots and the activation of BAT is an attractive strategy to combat obesity [ 10 ].…”

“…Cold exposure and exercise are methods by which BAT activation and beiging can be induced in humans [ 10 ]. A range of dietary compounds, including capsaicin, resveratrol, curcumin, green tea catechins, berberine, omega-3 polyunsaturated fatty acids and all-trans retinoic acid, have been examined in animals and humans as promoters of BAT thermogenesis and beiging with mixed results [ 4 ].…”