Browning of white adipose tissue: lessons from experimental models

Abstract

Beige or brite (brown-in-white) adipocytes are present in white adipose tissue (WAT) and have a white fat-like phenotype that when stimulated acquires a brown fat-like phenotype, leading to increased thermogenesis. This phenomenon is known as browning and is more likely to occur in subcutaneous fat depots. Browning involves the expression of many transcription factors, such as PR domain containing 16 (PRDM16) and peroxisome proliferator-activated receptor (PPAR)-γ, and of uncoupling protein (UCP)-1, which is the hallmark of thermogenesis. Recent papers pointed that browning can occur in the WAT of humans, with beneficial metabolic effects. This fact indicates that these cells can be targeted to treat a range of diseases, with both pharmacological and nutritional activators. Pharmacological approaches to induce browning include the use of PPAR-α agonist, adrenergic receptor stimulation, thyroid hormone administration, irisin and FGF21 induction. Most of them act through the induction of PPAR-γ coactivator (PGC) 1-α and the consequent mitochondrial biogenesis and UCP1 induction. About the nutritional inducers, several compounds have been described with multiple mechanisms of action. Some of these activators include specific amino acids restriction, capsaicin, bile acids, Resveratrol, and retinoic acid. Besides that, some classes of lipids, as well as many plant extracts, have also been implicated in the browning of WAT. In conclusion, the discovery of browning in human WAT opens the possibility to target the adipose tissue to fight a range of diseases. Studies have arisen showing promising results and bringing new opportunities in thermogenesis and obesity control.

Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

“…Another example is a transcription factor EBF2 (early B-cell factor 2) responsible for the PPARγ recruitment to genes crucial for the brown adipogenic processes [ 32 ]. PPARγ is crucial for UCP1 transcription during brown adipocytes differentiation; however, it is repressed in mature brown adipocyte, where a dominant role in the regulation of UCP1 transcriptional activity plays another member of the PPAR family—PPARα which also regulates the activity of genes involved in lipid oxidation [ 33 ].…”

Combating Obesity With Thermogenic Fat: Current Challenges and Advancements

“…Beige adipocytes have been reported to be transdifferentiated from white adipocytes (32,33) or directly differentiated from distinct progenitors including PDGFRα + (34), mural (35,36), or MyoD + progenitors (37). Numerous studies indicate that UCP1, one of the main regulators of adaptive thermogenesis, contributes to beige fat development (38)(39)(40). Moreover, classical beige adipocytes are governed by PRDM16 as well (41,42).…”

Browning of Adipose Tissue and Sirtuin Involvement

“…It has been proved that more than 50 transcriptional molecules have been identified and their action mechanisms have been defined necessary in the browning transcriptional process [35,56]. Among these, it is important to mention: PPARγ [50,57], several members of the bone morphogenic protein family (BMP) [35,58,59], peroxisome proliferatoractivated receptor gamma coactivator-1 alpha (PGC-1α), which is involved in mitochondrial biogenesis [30,33,35] and also some transcription factors, such as C/EBPα and PRDM16 [58,60,61]. Even though the current terminology stresses the differences in cell lineage and localization, the evidence suggests that the beige adipocytes function as true thermogenic brown adipocytes [35,47].…”