Human Biochemistry, Volume 1 - Murray R. 1993

Bioenergetics and Carbohydrate and Lipid Metabolism
Lipid Transport and Storage
Metabolic Transformations in Adipose Tissue and Fat Mobilization - The Role of Brown Adipose Tissue in Thermogenesis

Brown adipose tissue becomes a site of active METABOLISM primarily when the Organism needs to generate heat. This tissue is characterized by a High Metabolic Rate during arousal from hibernation (in certain animal species), upon cold exposure (non-shivering thermogenesis), as well as in newborn animals. In humans, this tissue plays a less prominent role, but studies have shown that in healthy individuals, brown Adipose tissue is quite active and likely mediates diet-induced thermogenesis, which may explain why some people do not gain weight despite a high caloric intake. Notably, in obese individuals, brown adipose tissue is either poorly developed or entirely absent. Brown adipose tissue is highly vascularized, its Cells contain a relatively high Abundance of Cell/35.html">Mitochondria and Cytochromes, and The activity of ATP synthase is remarkably low. Brown adipose tissue efficiently oxidizes both glucose and Fatty acids.

Norepinephrine released from sympathetic nerve terminals stimulates lipolysis in brown adipose tissue. In the mitochondria of these cells, oxidation and phosphorylation are uncoupled, as indicated by the lack of effect of dinitrophenol and the absence of Respiratory Control by ADP. In brown adipocytes, phosphorylation occurs at the substrate level, for example, at the step catalyzed by succinate thiokinase and during Glycolysis. Consequently, oxidation generates a large amount of heat, while only a small fraction of the free Energy is stored as ATP. From the perspective of the chemiosmotic theory, the proton gradient normally established across The inner mitochondrial membrane is dissipated in brown tissue; this function is performed by thermogenin, a protein that facilitates proton Transport Across the membrane. These concepts account for the apparent lack of effect of uncoupling agents (Fig. 26.10).

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Fig. 26.10. Thermogenesis in brown adipose tissue. During the operation of the Respiratory Chain, heat is generated concomitantly with proton translocation. When protons return to the inner mitochondrial compartment through the channel formed by thermogenin, ATP is not synthesized (unlike the process mediated by the F₁-ATP synthase system), but energy is instead dissipated as heat. Under resting conditions, when brown adipose tissue is not stimulated, H⁺ flux through the thermogenin channel is inhibited by purine NUCLEOTIDES. This inhibition is relieved by norepinephrine, which stimulates The production of free fatty acids (FFAs) and acyl-CoA. Note the dual role of acyl-CoA, which not only enhances thermogenin activity but also supplies reducing equivalents for the respiratory chain. (⊕) positive and (⊝) negative regulatory effects.

References

Brown М. S., Goldstein J. L. Lipoprotein metabolism in the macrophage: Implications for Cholesterol deposition in atherosclerosis, Annu. Rev. Biochem., 1983, 52, 223.

Cryer A. Tissue lipoprotein lipase activity and its action in lipoprotein metabolism, Int. J. Biochem., 1981, 13, 525.

Eisenberg S. Lipoproteins and lipoprotein metabolism, Klin. Wochenschr., 1983, 61, 119.

Fain J. N. Hormonal Regulation of lipid mobilization from adipose tissue. Page 119 in: Biochemical Actions of Hormones. Vol. 7. Litwack G. (ed.), Academic Press, 1980.

Fielding C. J., Fielding P. E. Metabolism of cholesterol and lipoproteins. Page 404 in: BIOCHEMISTRY OF Lipids and Membranes; Vance D. E., Vance J. E. (ed.), Benjamin/Cummings, 1985.

Himms-Hagen J. Brown adipose tissue metabolism and thermogenesis, Annu. Rev. Nutr., 1985, 5, 69.

Krauss R. M. Regulation of high density lipoprotein level, Med. Clin. North Am., 1982, 66, 403.

Lieber C. S. Alcohol and the Liver: Metabolism of ethanol, metabolic effects and Pathogenesis of injury, Acta. Med. Scand. (Suppl), 1985, 703, 11.

Sparks J. D., Sparks C. E. Apolipoprotein В and lipoprotein metabolism, Adv. Lipid Res., 1985, 21, 1.