Thermogenic tissues

Thermodynamics and Reverse Electron Flow Thermogenic Tissues... 

BOX 18-C USING METABOLISM TO GENERATE HEAT THERMOGENIC TISSUES... 

Thyroid hormones are intimately involved in regulating the basal metabolic rate. Liver tissue of animals given excess thyroxine shows an increased rate of 02 consumption and increased heat output (thermogenesis), but the ATP concentration in the tissue is normal. Different explanations have been offered for the thermogenic effect of thyroxine. One is that excess thryroxine causes uncoupling of oxidative phosphorylation in mitochondria. How could such an effect account for the observations Another explanation suggests that the thermogenesis is due to an increased rate of ATP utilization by the thyroxine-stimulated tissue. Is this a reasonable explanation Why ... 

Only in three tissues — in two plant tissues (the Arum lily flower and the skunk cabbage spadix) and in mammalian brown adipose tissue — has a direct thermogenic role of mitochondria been substantiated. 

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. 

With our present understanding, the thermogenic qualities of brown adipose tissue mitochondria are a consequence of the existence in the mitochondrial inner membrane of a polypeptide, thermogenin, uniquely [13-15] found in brown adipose tissue. (For technical and historical reasons, thermogenin is also known under several other names, such as the GDP-binding protein, the 32000 protein, the purine-nucleotide-binding protein (NbP), the uncoupling protein (UCP), the proton conductance pathway, etc.)... 

When mitochondria are isolated and tested in media which only contain osmotic support (sucrose or KCl) and a buffer (and Mg, Pj and EDTA, if necessary), they respire rapidly on substrates such as succinate or glycerol-3-phosphate (citrate, 2-oxoglutarate and malate are poor substrates in brown fat mitochondria from most species, as the substrate permeases are poorly developed [16]). This rapid respiration is seen in Fig. 10.2. This observation was initially made even before the thermogenic function of brown adipose tissue was known [17]. When R. Em. Smith had established that heat production was the function of the tissue [18], an intrinsic uncoupled state of the mitochondria [19,20] could be understood as the means of heat production, the intensity of which would be limited only by substrate supply [21]. However, Horwitz et al. [21a] found that addition of the artificial uncoupler DNP could potentiate the respiration of the tissue, and the conclusion had to be that the mitochondria — although uncoupled when isolated — were coupled in situ. 

Himms-Hagen J, Cui J, Danforth E Jr, et al. Effect of CL-316,243, a thermogenic P3-agonist, on energy balance and brown and white adipose tissues in rats. Am J Physiol 1994 266 R1371-R1382. 

---