Brown fat fuel utilization and thermogenesis

Abstract

Brown adipose tissue (BAT) dissipates energy as heat to maintain optimal thermogenesis and to contribute to energy expenditure, in rodents and possibly humans. The energetic processes executed by BAT require a readily available fuel supply, which includes glucose and fatty acids (FAs). FAs become available by cellular uptake, de novo lipogenesis, and from multilocular lipid droplets in brown adipocytes. BAT also possesses a great capacity for glucose uptake and metabolism, and an ability to regulate insulin sensitivity. These properties make BAT an appealing target for the treatment of obesity, diabetes and other metabolic disorders. Recent research has revealed a better understanding of the processes of fuel utilization carried out by brown adipocytes, which is the focus of the current review.

Role of Brown Fat in Lipoprotein Metabolism and Atherosclerosis

“…This results in activation of adenylyl cyclase to produce cyclic AMP that activates protein kinase A to phosphorylate the lipolytic enzymes adipose triglyceride lipase, hormone-sensitive lipase, and monoglycerol lipase, leading to increased intracellular lipolysis. 29 FA that are released subsequently enter the mitochondria where they are broken down into substrates for the citric acid cycle, leading to activation of the electron transport chain and uncoupled respiration through UCP-1 that results in the generation of heat instead of ATP. 12 Of note, the use of the PET tracer […”

“…33,34 After its uptake by the glucose transporter-1 and glucose transporter-4, 29,30 glucose is used for both de novo lipogenesis and ATP generation that supports general adipocyte function. 35 Indeed, BAT activation increases the expression of genes involved in glycolysis and the pentose phosphate pathway; pathways that provide ATP and reducing equivalents for de novo lipogenesis, respectively.…”

Insufficient glucose supply is linked to hypothermia upon cold exposure in high-fat diet-fed mice lacking PEMT

“…On the other hand, HF-fed Pemt Ϫ / Ϫ mice have choline defi ciency (unpublished observations), which might reduce acetylcholine ( 32 ), a well-known vascular dilator ( 33 ). BAT consumes not only fatty acids but also large amounts of glucose from blood ( 34,35 ). Cold exposure profoundly increases (by 95-fold) glucose uptake by BAT in rats ( 36 ).…”

GADD45γ regulates the thermogenic capacity of brown adipose tissue

“…norepinephrine signaling | transcriptional regulation | adrenergic response | nuclear receptors T hrough the regulated dissipation of energy as heat (thermogenesis), brown adipose tissue (BAT) can increase total body energy expenditure and impact adiposity (1,2). In humans, activation of BAT by exposure to cold or pharmacologically leads to body-fat loss (3)(4)(5).…”

“…BAT oxidative capacity and the levels of UCP1 are regulated at the transcriptional level and are increased by exposure to cold, via the sympathetic nervous system-dependent release of norepinephrine. Norepinephrine, as well as other activators of thermogenesis, induces an intracellular signaling pathway that includes protein kinases A and G (PKA and PKG), the MAPK p38, and the transcriptional regulator peroxisome proliferator-activated receptorgamma coactivator 1 α (PGC-1α) and leads to the enhanced expression of oxidative metabolism genes and Ucp1 (1,2,7,8).…”