Cannon, Barbara, and Jan Nedergaard. Brown Adipose Tissue: Function and Physiological Significance. Physiol Rev 84: 277–359, 2004; 10.1152/physrev.00015.2003.—The function of brown adipose tissue i...

Brown Adipose Tissue: Function and Physiological Significance

Using positron-emission tomography (PET), we found that cold-induced glucose uptake was increased by a factor of 15 in paracervical and supraclavicular adipose tissue in five healthy subjects. We obtained biopsy specimens of this tissue from the first three consecutive subjects and documented messenger RNA (mRNA) and protein levels of the brown-adipocyte marker, uncoupling protein 1 (UCP1). Together with morphologic assessment, which showed numerous multilocular, intracellular lipid droplets, and with the results of biochemical analysis, these findings document the presence of substantial amounts of metabolically active brown adipose tissue in healthy adult humans.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa0808949

Functional brown adipose tissue in healthy adults.

The contention that brown adipose tissue is absent in adult man has meant that processes attributed to active brown adipose tissue in experimental animals (mainly rodents), i.e., classical nonshivering thermogenesis, adaptive adrenergic thermogenesis, diet-induced thermogenesis, and antiobesity, should be either absent or attributed to alternative (unknown) mechanisms in man. However, serendipidously, as a consequence of the use of fluorodeoxyglucose positron emission tomography (FDG PET) to trace tumor metastasis, observations that may change that notion have recently been made. These tomography scans have visualized symmetrical areas of increased tracer uptake in the upper parts of the human body; these areas of uptake correspond to brown adipose tissue. We examine here the published observations from a viewpoint of human physiology. The human depots are somewhat differently located from those in rodents, the main depots being found in the supraclavicular and the neck regions with some additional paravertebral, mediastinal, para-aortic, and suprarenal localizations (but no interscapular). Brown adipose tissue activity in man is acutely cold induced and is stimulated via the sympathetic nervous system. The prevalence of active brown adipose tissue in normal adult man can be only indirectly estimated, but it would seem that the prevalence of active brown adipose tissue in the population may be at least in the range of some tens of percent. We conclude that a substantial fraction of adult humans possess active brown adipose tissue that thus has the potential to be of metabolic significance for normal human physiology as well as to become pharmaceutically activated in efforts to combat obesity.

Unexpected evidence for active brown adipose tissue in adult humans

The goal of this review is to place the exciting advances that have occurred in our understanding of the molecular biology of the types 1, 2, and 3 (D1, D2, and D3, respectively) iodothyronine deiodinases into a biochemical and physiological context. We review new data regarding the mechanism of selenoprotein synthesis, the molecular and cellular biological properties of the individual deiodinases, including gene structure, mRNA and protein characteristics, tissue distribution, subcellular localization and topology, enzymatic properties, structure-activity relationships, and regulation of synthesis, inactivation, and degradation. These provide the background for a discussion of their role in thyroid physiology in humans and other vertebrates, including evidence that D2 plays a significant role in human plasma T3 production. We discuss the pathological role of D3 overexpression causing “consumptive hypothyroidism” as well as our current understanding of the pathophysiology of iodothyronine deiodination during illness and amiodarone therapy. Finally, we review the new insights from analysis of mice with targeted disruption of the Dio2 gene and overexpression of D2 in the myocardium. (Endocrine Reviews 23: 38–89, 2002)

Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases.

Thermogenic mechanisms in brown fat.

The amount and distribution of brown adipose tissue (BAT) in healthy adult human subjects remain uncertain. BAT has been described in patients with pheochromocytoma. This pathological situation was chosen to try to characterize human BAT using both morphological and biochemical criteria. Typical multilocular brown adipocytes were observed; the cytoplasm of these adipocytes was filled with mitochondria with numerous tightly packed cristae, as in rat or hamster BAT. Isolated mitochondria exhibited a loose respiratory coupling sensitive to guanosine diphosphate; the chloride conductance of these mitochondria was reduced by the addition of this nucleotide. It is concluded that in patients with pheochromocytoma, there is a large amount of a tissue around the adrenal glands and kidneys which fullfills the ultrastructural and biochemical criteria for a BAT.

Ultrastructural and biochemical characterization of human brown adipose tissue in pheochromocytoma.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2884%2980120-9

Noradrenaline controls the concentration of the uncoupling protein in brown adipose tissue

Factors affecting brown adipose tissue activity in animals and man

The aim of the present study was to investigate the role of the sympathetic nervous system in the trophic response of brown adipose tissue (BAT) to chronic cold exposure The hyperplasia and the development of the mitochondria characterizing this response are usually considered as mainly controlled by the sympathetic activity in BAT, but this has never been clearly demonstrated In the present work rats were sympathectomized by chronic administration of guanethidine and then exposed to cold during two weeks The treatment induced a strong reduction of the noradrenaline content of BAT The trophic response of the tissue to cold was largely impaired: no increase of the tissue weight, weak increase in the DNA, protein, and phospholipid content of the tissue The development of the mitochondria was almost abolished The increase in the proportion of the 32,000-dalton protein, a protein which regulates heat production by BAT, was suppressed and the GDP-binding to mitochondria, which is an index of BAT thermogenic capacity, was not increased as in normal cold-adapted rats The ultrastructure of the tissue remained the same as in warm-adapted animals It is concluded that the sympathetic nervous system plays an essential role in the control of the trophic response of BAT to the cold

Impairment of trophic response of brown fat to cold in guanethidine-treated rats.

The heparin-releasable LP lipase activity of BAT (brown adipose tissue), and the TG (triglyceride) content of plasma were determined in normal and hypothyroid rats during early post-natal development. The TG content of plasma increased sharply after the onset of suckling and decreased during the weaning period in normal rats, while it stayed at a high level in hypothyroid rats. LP lipase activity was maximal during the perinatal period and decreased later, being practically undetectable in one month old control animals; in contrast, LP lipase activity was still present in cretin rats at this age. The effects of several forms of treatment were also tested in weaned rats: a high-fat diet was not able to maintain the high LP lipase activity of suckling rats, but the activity was high if the animals were bred at a cold temperature. Thyroxine injections had no effect. These results are discussed in terms of the possible factors regulating the LP lipase activity in BAT.

The lipoprotein lipase activity of brown adipose tissue during early post-natal development of the normal and hypothyroid rat.

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