Review
Brown fat fuel utilization and thermogenesis

https://doi.org/10.1016/j.tem.2013.12.004Get rights and content

Highlights

  • BAT is a very energy-expending tissue, undergoing high levels of thermogenesis and β-oxidation.

  • Brown adipose tissue utilizes both glucose and fatty acids as fuel.

  • The regulation of these fuels occurs via availability, sensing, uptake and utilization.

  • All of the above may be potential targets for increasing BAT activation and combating obesity.

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 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 provided a better understanding of the processes of fuel utilization carried out by brown adipocytes, which is the focus of the current review.

Section snippets

Significance of brown fat

The main function of BAT is to dissipate energy in the form of heat, a property driven by the presence of the mitochondrial protein UCP1 (uncoupling protein 1) that uncouples mitochondrial respiration. BAT is also densely innervated by the sympathetic nervous system (SNS) and is highly vascularized [1]. The thermogenic capacity of BAT may be important for heat production in newborns, essential for rodents and hibernating mammals, and possibly helps burn excess dietary energy consumption.

Imaging

Glucose utilization by BAT

The use of positron emission tomography–computed tomography (PET-CT) imaging with the tracer fluorodeoxyglyucose (FDG) allows imaging of metabolically active BAT in humans that readily takes up glucose. Experiments in adult humans demonstrated that the rate of cold-activated glucose uptake exceeded that of insulin-stimulated glucose uptake in skeletal muscle. Specifically, glucose uptake after cold-exposure was increased 12-fold in BAT, and was correlated with an increase in whole-body energy

FAs as fuel for BAT

FAs fulfill a wide variety of roles in physiology (reviewed in 34, 35), including providing structural support in cell membranes, affecting the activities of particular transcription factors, and activating GPCRs. After a meal, FAs and glucose are stored in the adipose as triglycerides (TGs) and, when energy is depleted, TGs are degraded to release FAs via the process of lipolysis. Dietary nutrients are also stored in liver, muscle, and heart, but these are relatively short-lived compared to

Signaling pathways regulating BAT fuel utilization

For BAT to effectively burn extra calories it needs a readily available fuel supply, as well as activation of its energy-expending capacity for β-oxidation and thermogenesis. The classic method of activating BAT energy expenditure is via the SNS. Although this pathway and its synergistic activation of BAT with the thyroid hormone system are well characterized recent studies have described several novel factors and signaling pathways (such as fibroblast growth factor 21, FGF21), cardiac

Concluding remarks and future perspectives

Given that obesity results from an energy imbalance leading to caloric overload, WAT must appropriately respond by storing excess energy in lipid droplets. The ability of adipose tissue to undertake this role or the ‘adipose expandability’ of a given person [101] may be a factor predisposing to the metabolic disturbances with obesity, which include ectopic lipid-deposition in tissues such as skeletal muscle and liver, leading to lipotoxicity. If agents can (i) specifically increase SNS

Acknowledgments

The authors wish to thank E. Caniano for administrative assistance, the reviewers for thoughtful and thorough comments, and Y.M. Kwon for editing of the manuscript. Elements of some figures were produced using Servier Medical Art (http://www.servier.com). This work was supported in part by National Institutes of Health (NIH) grants R01 DK077097 (to Y-H.T.) and P30 DK036836 (Diabetes Research Center of the Joslin Diabetes Center), a research grant from the American Diabetes Association and

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