The Role of Physical Exercise to Improve the Browning of White Adipose Tissue via POMC Neurons

Abstract

Obesity is a public health issue that affects more than 600 million adults worldwide. The disease is characterized by fat accumulation, mainly in the abdominal area. The human body is mainly composed of two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT); however, the browning process generates a different type of brown fat-like adipocyte in WAT, which similar to BAT has thermogenic capacity by activating UCP-1. The hypothalamic arcuate nucleus plays an important role in WAT browning via POMC neurons, which are influenced by synergistic insulin and leptin signaling. On the other hand, stimulation of AgRP neurons suppresses WAT browning. The hypothalamic inflammatory process that occurs in obesity impairs insulin and leptin signaling in this tissue and, consequently, can decrease WAT browning. In addition, practicing physical exercise may be a great strategy for triggering the browning process since it reduces hypothalamic inflammation and increases POMC neurons gene expression. Moreover, physical exercise stimulates irisin gene expression, which has an important impact on thermogenesis, which in turn culminates in increased gene expression of proteins such as UCP-1 and Cidea, which are related to WAT browning. Furthermore, thermogenetic activation of WAT leads to increased energy expenditure, favoring obesity treatment. Therefore, this mini-review aimed to highlight the most recent studies that link the control of hypothalamic activity with the browning metabolism of adipose tissue in response to physical exercise.

Brown Adipose Tissue Energy Metabolism in Humans

“…Third, BAT-derived circulating factor such as IL-6 ( 246 ) or the recently discovered 12,13 diHOME ( 247 ) have been implicated in systemic metabolic improvement in mice. Fourth, exercise may lead to improved leptin and insulin signaling in the brain, with enhanced pro-opio-melanocortin neurons activation leading to WAT browning ( 241 ). However, exercise has long been shown to reduce cold-induced thermogenesis and cold acclimation in rats ( 248 , 249 ), likely because heat produced by exercise down-regulates the sympathetic stimulatory output signal to BAT.…”

Adropin and Irisin in Patients with Cardiac Cachexia

“…10 have added to the studies in the area the results of the research on two proteins that act on the mechanisms of energetic homeostasis – adropin 11 and irisin. 12 Those authors have found that the concentration of those proteins differed in 44 patients with cachexia (body mass index 19.9; standard deviation 1.12) as compared to that of 42 patients without cachexia (body mass index 29.2; standard deviation 4.25). On multivariate logistic regression, adropin remained associated with cachexia, despite the low hazard ratio.…”

Is Exercise a Match for Cold Exposure? Common Molecular Framework for Adipose Tissue Browning

“…Though UCP1 is only constitutively active in BAT, continuous betaadrenergic stimulation can lead to the recruitment or conversion of brown adipocyte-like cells among WAT depots, a process referred to as "beigeing" or "browning" [19]. WAT browning may also occur through central nervous system pathways via the suppression of agouti-related protein (AgRP) neurons and activation of proopiomelanocortin (POMC) neurons, the mechanisms of which have been reviewed extensively elsewhere [42].…”

“…Physical exercise improves leptin and insulin signaling via decreased hypothalamic inflammation [189] and by regulating several proteins involved in their signal transduction pathways, thereby enabling leptin and insulin to synergistically activate POMC [190]. Restoration of insulin and leptin signaling in POMC neurons enhances WAT browning by further increasing SNS activity [42]. Thus, exercise potentiates BAT activation and beige fat induction independently of a thermal impetus and overall through increased SNS activation.…”