An insight into brown/beige adipose tissue whitening, a metabolic complication of obesity with the multifactorial origin

Abstract

Brown adipose tissue (BAT), a thermoregulatory organ known to promote energy expenditure, has been extensively studied as a potential avenue to combat obesity. Although BAT is the opposite of white adipose tissue (WAT) which is responsible for energy storage, BAT shares thermogenic capacity with beige adipose tissue that emerges from WAT depots. This is unsurprising as both BAT and beige adipose tissue display a huge difference from WAT in terms of their secretory profile and physiological role. In obesity, the content of BAT and beige adipose tissue declines as these tissues acquire the WAT characteristics via the process called “whitening”. This process has been rarely explored for its implication in obesity, whether it contributes to or exacerbates obesity. Emerging research has demonstrated that BAT/beige adipose tissue whitening is a sophisticated metabolic complication of obesity that is linked to multiple factors. The current review provides clarification on the influence of various factors such as diet, age, genetics, thermoneutrality, and chemical exposure on BAT/beige adipose tissue whitening. Moreover, the defects and mechanisms that underpin the whitening are described. Notably, the BAT/beige adipose tissue whitening can be marked by the accumulation of large unilocular lipid droplets, mitochondrial degeneration, and collapsed thermogenic capacity, by the virtue of mitochondrial dysfunction, devascularization, autophagy, and inflammation.

High-Fat-High-Fructose Diet Elicits Brown Adipocyte Dysfunction through miRNA-103 Induced miRNA Biogenesis Pathway

“…In contrast to short-term diet exposure, reduced UCP1 and PGC1α expression levels under 12 weeks of HFHFD exposure (Figure 2a) revealed that the dissipating capacity of BAT might have been impaired in profound obese or diabetic conditions. We predict that this may be pivoting from an adaptive state to an overburdened one, which aligns with several previous studies where mice were subjected to HFD for longer time periods [29,42]. Specifically, these studies demonstrated that the significant body weight gain over time due to high-fat diet challenge diminishes UCP1 and PCG1α expression in BAT [43].…”

“…To elucidate the underpinning molecular mechanisms mediating the diet-induced BAT dysfunction across different time periods, we then investigated key biomarkers for thermogenesis and apoptosis. As whitened BAT is typically accompanied by diminished UCP1 and PGC1α thermogenic biomarkers [29], we first evaluated their expressions in the BAT. UCP1 and PGC1α were indeed altered in the BAT of mice fed an HFHFD (Figure 2).…”

“…BAT whitening has been described to be marked by the accumulation droplets and compromised thermogenic capacity [29]. BAT from HFH showed increased visible whitening after 12 weeks compared to LFD fed mi This whitening became more pronounced after 20 weeks of HFHFD.…”

Progress and obstacles in transplantation of brown adipose tissue or engineered cells with thermogenic potential for metabolic benefits

“…BAT can function as a “heat production factory”, with the UCP1 protein in mitochondria inner membrane mediating uncoupling thermogenesis when fueling lipids and glucose ( 34 ). However, the thermogenic potential of BAT can be significantly impaired with aging or the development of obesity, which is called the whitening of BAT ( 35 ). In elderly obese individuals, BAT in specific anatomical regions showed reduced content with less vascularization and lightened brown color.…”

Brown adipose tissue: can it keep us slim? A discussion of the evidence for and against the existence of diet-induced thermogenesis in mice and men

“…Thus, if these results are recalculated on a whole-tissue (depot) basis, there may not be any lowering of UCP1 amounts at all (but such calculations are not generally made). The mice with whitened brown adipose tissue are also reported to present with lower metabolism (energy expenditure) [44,45], but this is generally expressed-physiologically erroneously-per body weight, a calculation process that automatically makes obese mice demonstrate low metabolic rate (as has been discussed elsewhere, e.g. [46][47][48][49]).…”