Molecular and cellular regulation of thermogenic fat

Abstract

Thermogenic fat, consisting of brown and beige adipocytes, dissipates energy in the form of heat, in contrast to the characteristics of white adipocytes that store energy. Increasing energy expenditure by activating brown adipocytes or inducing beige adipocytes is a potential therapeutic strategy for treating obesity and type 2 diabetes. Thus, a better understanding of the underlying mechanisms of thermogenesis provides novel therapeutic interventions for metabolic diseases. In this review, we summarize the recent advances in the molecular regulation of thermogenesis, focusing on transcription factors, epigenetic regulators, metabolites, and non-coding RNAs. We further discuss the intercellular and inter-organ crosstalk that regulate thermogenesis, considering the heterogeneity and complex tissue microenvironment of thermogenic fat.

Dynamic changes of immunocyte subpopulations in thermogenic activation of adipose tissues

“…Some non-coding RNAs, such as miRNAs, regulate thermogenesis by binding to the UTR regions of target mRNAs. LncRNAs interact with other important transcription factors such as PGC1a, Early B-cell factor 2 (EBF2), and PPARγ to modulate energy expenditure both in brown and beige adipocytes ( 13 ).…”

“…Adipose tissues primarily consist of adipocytes and stromal vascular fraction (SVF) cells, including immune cells, endothelial cells, mesenchymal stem cells, and neuronal cells, all of which dynamically interact to maintain the balance of the adipose microenvironment ( 13 ). Upon cold exposure, thermogenic brown/beige adipocytes can be regulated by alterations in the immune microenvironment, which is composed of multiple immune cells and stromal cells ( 14 , 15 ).…”

Role of Spexin in White Adipose Tissue Thermogenesis under Basal and Cold-Stimulated Conditions

“…Beige adipocytes can dissipate energy into heat through the activity of the mitochondrial Uncoupling protein 1 (UCP1). Under cold and/or pharmacological conditions (β3-adrenergic receptor activation), white adipocytes can become beige adipocytes [18,19]. This process is known as browning, and its activation has widely been accepted as an effective strategy to treat both obesity and metabolic diseases.…”

“…During this differentiation, PRDM16, a transcriptional coregulator, interacts with several DNA-binding transcriptional factors such as PPARγ and the C/EBPs family and induces PGC1α and COX8B expression, triggering mitochondrial biogenesis and mitochondrial electron transport activation, respectively. This results in increased UCP1 expression and activity [19,24].…”

Rabbit Meat Extract Induces Browning in 3T3−L1 Adipocytes via the AMP−Activated Protein Kinase Pathway

“…White adipocytes store energy in the form of triglycerides, which are stored in unilocular lipid droplets, whereas brown adipocytes have multilocular lipid droplets and abundant mitochondria that dissipate energy [7]. A third type, termed as beige adipocytes, has the characteristics of brown adipocytes and is formed in white adipose tissue [7,8]. The ability of white adipocytes to convert to the brown adipocyte phenotype in response to specific stimuli, such as exposure to cold temperatures or beta−adrenergic stimulation, is being studied for obesity treatment [9,10].…”