Non-shivering Thermogenesis Signalling Regulation and Potential Therapeutic Applications of Brown Adipose Tissue

Abstract

In mammals, thermogenic organs exist in the body that increase heat production and enhance energy regulation. Because brown adipose tissue (BAT) consumes energy and generates heat, increasing energy expenditure via BAT might be a potential strategy for new treatments for obesity and obesity-related diseases. Thermogenic differentiation affects normal adipose tissue generation, emphasizing the critical role that common transcriptional regulation factors might play in common characteristics and sources. An understanding of thermogenic differentiation and related factors could help in developing ways to improve obesity indirectly or directly through targeting of specific signalling pathways. Many studies have shown that the active components of various natural products promote thermogenesis through various signalling pathways. This article reviews recent major advances in this field, including those in the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA), cyclic guanosine monophosphate-GMP-dependent protein kinase G (cGMP-AKT), AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), transforming growth factor-β/bone morphogenic protein (TGF-β/BMP), transient receptor potential (TRP), Wnt, nuclear factor-κ-light-chain-enhancer of activated B cells (NF-κΒ), Notch and Hedgehog (Hh) signalling pathways in brown and brown-like adipose tissue. To provide effective information for future research on weight-loss nutraceuticals or drugs, this review also highlights the natural products and their active ingredients that have been reported in recent years to affect thermogenesis and thus contribute to weight loss via the above signalling pathways.

Semaglutide (GLP‐1 receptor agonist) stimulates browning on subcutaneous fat adipocytes and mitigates inflammation and endoplasmic reticulum stress in visceral fat adipocytes of obese mice

“…Lpl mediates fatty acid uptake from lipoproteins, which augments de novo lipogenesis, blocking sWAT browning 37 . In addition, increased DIO mice's Hsl enhanced lipolysis of their lipid reservoir and adipocyte enlargement 38 . Particularly, a similar experimental design showed hepatic steatosis enhancement, suggesting DIO mice lipotoxicity and limited capacity for adipocyte expansion 12 …”

Impacts of essential amino acids on energy balance

“…However, whether mTOR signaling mediates the effects of these two diets in energy balance remains unclear. Based on the available literature, we speculate that mTOR signaling may play a role in energy homeostasis under these two diets [ 164 , 165 ]. On the one hand, the activation of mTOR signaling pathway in the hypothalamus reduces food intake via inhibiting AgRP and NPY [ 129 , 166 ].…”

The evolving view of thermogenic fat and its implications in cancer and metabolic diseases

“…It implies that the thermogenic function of brown adipose tissue (BAT) is completely activated at birth, which is of supreme importance to newborn animals because neonates of many larger animals including humans are based on the non-shivering thermogenesis of BAT to maintain normal body temperature. 25 – 27 Pulse-chase lineage tracing studies suggest that most brown fat cells originate from precursor cells in the embryonic mesoderm developmentally, and these precursors transiently express somite markers, such as paired-box protein 3 (Pax3), myogenic factor 5 (Myf5), and mesenchyme homeobox 1 (Meox1), engrailed 1 (En1). 17 , 28 In rodents, the major BAT depots are distributed in the interscapular region covering axillary, interscapular, and cervical pads embedded in and around deep back muscles.…”