Thermogenesis, mitochondrial

Brown adipose tissue is the site of nonshivering thermogenesis. It is found in hibernating and newborn animals and is present in small quantity in humans. Thermogenesis results from the presence of an uncouphng protein, thermogenin, in the inner mitochondrial membrane. 

The major types of adipose tissue are (1) white adipose tissue, which manufactures, stores, and releases lipid and (2) brown adipose tissue, which dissipates energy via uncoupled mitochondrial respiration. Obesity research includes evaluation of the activity of adrenergic receptors and their effect on adipose tissue with respect to energy storage and expenditure or thermogenesis. 

Ernster, L. (ed.), Bioenergetics. Amsterdam Elsevier, 1984. A collection of reviews covering electron transport, the ATP-synthase, translocation of ions across the mitochondrial inner membrane, thermogenesis in brown fat, and other topics in bioenergetics. 

Within the last decade we have obtained a tentative concept of the molecular basis for this mammalian mitochondrial thermogenesis, and we know that in contrast to the thermogenic plant mitochondria, substrate oxidation in brown adipose tissue mitochondria is basically energy conserving, with proton extrusion occurring [5], with respiratory control, and with an ability, in principle, to capture the chemical energy in the form of ATP. 

Fig. 10.1. The thermogenin concept. In the model for mitochondrial thermogenesis presented here, the thermogenesis is assumed to originate from the action of the brown fat-specific protein, thermogenin. Thermogenin acts as an OH conductor, regulated by cytosolic nucleotides (here shown as ATP) and by the so-called mediator (see Section 5). The OH neutralizes the H electrochemical gradient created by respiration, and substrate oxidation occurs unhampered by this gradient and without energy conservation. (Adapted from Ref. 6.)...

Fig. 10.13. A sketch of the possible interactions of free fatty acids and their derivatives with brown fat mitochondria. The sketch illustrates some of the candidates for the mediator of thermogenesis (i.e., the substance or process that will activate thermogenin (alt. another site of the mitochondrial membrane) even in the presence of the inhibitory cytosohc nucleotides). Common for the candidates shown here is that they are formed subsequent to the activation of lipolysis of the stored triglycerides (TG) by norepinephrine (NE) via cAMP-dependent processes. The candidates illustrated are free fatty acids (FFA), interacting (1) with the purine-nucleotide binding site on thermogenin, (2) with another site on thermogenin, (3) with another protein than thermogenin, or (4) directly with the membrane, and the acyl-CoAs, interacting (5) specifically with the purine-nucleotide binding site on thermogenin, or (6) unspecifically with the membrane. For discussion, see Section 5.

NPY injection into the PVN of the hypothalamus causes a decrease in brown adipose tissue (BAT) thermogenesis as indicated by the measurement of BAT mitochondrial GDP binding and uncoupling protein mRNA (Billington et al., 1991, 1994). This occurs even when NPY-treated animals are pair-fed, which involves allowing... 

Leptin acts on receptors in the arcuate nucleus of the hypothalamus, causing the release of anorexigenic peptides, including a-MSH, that act in the brain to inhibit eating. Leptin also stimulates sympathetic nervous system action on adipocytes, leading to uncoupling of mitochondrial oxidative phosphorylation, with consequent thermogenesis. 

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