guanosine-diphosphate and Atrophy

Interscapular brown adipose tissue (BAT) of capsaicin-desensitized (Cap-Des) rats is atrophied, having a lower wet weight, a reduced total protein content, and as little as 10% of the normal content of uncoupling protein (UCP). Because the mitochondrial concentration of UCP, relative to other mitochondrial proteins, is not altered in Cap-Des rats, it is concluded that most of the mitochondria of BAT of Cap-Des rats have been lost. Consistent with this interpretation is a reduction of almost 40% of the overall thermogenic response to infused norepinephrine by anesthetized Cap-Des rats. Feeding a palatable diet had a delayed thermogenic effect and no trophic effect on BAT of Cap-Des rats. Food selection and intake were normal in Cap-Des rats, and diet-induced weight gain was the same as in control rats. Exposure of Cap-Des rats to cold for 1 or 7 days exerted a normal thermogenic effect on BAT but a delayed trophic effect. The cold-induced increase in thyroxine 5'-deiodinase in BAT occurred normally. Cap-Des rats were hypothermic at 1 day but normothermic by 7 days of cold exposure. The concentration of thyroid hormones in their blood was normal. It is suggested that the depletion of sensory neuropeptides in BAT presumed to be brought about by Cap-Des results either in loss of a trophic influence on mitochondriogenesis in BAT or in lack of an inhibitory influence on mitochondrial breakdown in BAT and leads to atrophy of BAT in rats living at 26 degrees C and an impaired response to stimulation by diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adipose Tissue, Brown; Animals; Atrophy; Body Temperature Regulation; Capsaicin; Carrier Proteins; Cell Survival; Cold Temperature; Diet; Guanosine Diphosphate; Ion Channels; Male; Membrane Proteins; Mitochondria; Mitochondrial Proteins; Neurons, Afferent; Norepinephrine; Rats; Rats, Inbred Strains; Uncoupling Protein 1

In euthyroid mice, a 48-h fast caused brown fat (BAT) atrophy characterized by loss of tissue proteins, succinate dehydrogenase (SDH), and a significant reduction in mitochondrial uncoupling protein (UCP) content. Chemical sympathectomy and surgical denervation failed to mimic the changes in BAT protein and SDH contents observed after food deprivation. However, suppression of sympathetic activity could account for the loss of UCP from the mitochondria. In mice made hyperthyroid by repeated triiodothyronine injections, losses of tissue SDH and proteins caused by food deprivation or surgical denervation were markedly suppressed, while the loss of UCP from the mitochondria remained unchanged. These results suggest that reduced sympathetic activity to BAT in fasted mice is not the exclusive cause of the tissue atrophy and that thyroid hormones may play a role in the control of brown fat atrophy in mice.

Topics: Adipose Tissue, Brown; Animals; Atrophy; Body Weight; Denervation; Energy Metabolism; Food Deprivation; Guanosine Diphosphate; Male; Mice; Mice, Inbred Strains; Mitochondria; Neurons; Succinate Dehydrogenase; Sympathectomy, Chemical; Thyroid Gland; Thyroid Hormones

The thermogenic activity and capacity of brown adipose tissue were determined in mice during lactation and after weaning. There was a marked fall during lactation in the mitochondrial content of the tissue, and in GDP binding and the specific mitochondrial concentration of uncoupling protein. The lactation-induced functional atrophy of brown adipose tissue was fully reversible after weaning; mitochondrial content and the mitochondrial concentration of uncoupling protein were both restored, although GDP binding was not normalized.

Topics: Adipose Tissue, Brown; Animals; Atrophy; Carrier Proteins; Electron Transport Complex IV; Female; Guanosine Diphosphate; Ion Channels; Lactation; Membrane Proteins; Mice; Mitochondria; Mitochondrial Proteins; Organ Size; Pregnancy; Proteins; Uncoupling Protein 1

The objectives of this study were to evaluate the rate at which brown adipose tissue (BAT) from mice atrophies when its thermogenic activity is suppressed during fasting or exposure to a thermoneutral environment (33 degrees C) and whether such atrophy is accompanied by loss from BAT mitochondria of "thermogenin," the GDP binding protein associated with the calorigenic proton conductance pathway. Atrophy of mouse BAT was characterized by rapid loss of protein but unchanged tissue DNA content. The rate of protein loss varied from 2 to 6 mg protein/day depending on the environmental and feeding status of the mice. In synchrony with tissue protein loss, there was a marked reduction in the tissue content of mitochondrial proteins and of thermogenin, measured by immunoassay. However, the concentration of thermogenin in isolated mitochondria was unchanged by fasting or exposure of the mice to 33 degrees C for 48 h. By contrast, marked reduction in [3H]GDP binding to isolated mitochondria were observed after exposure of the mice to 33 degrees C. Mice acclimated at 4 but not those acclimated at 21 degrees C showed reduction in GDP binding to isolated mitochondria during fasting. These results clearly indicate that changes in purine nucleotide binding to isolated mitochondria can occur in the absence of changes in the mitochondrial concentration of thermogenin. Thus rapid decrease in BAT thermogenic capacity (e.g., during fasting or 33 degrees C exposure) appears dependent on extensive loss of tissue protein, probably whole mitochondria, rather than rapid and selective removal of thermogenin from the mitochondria.

Topics: Acclimatization; Adipose Tissue, Brown; Animals; Atrophy; Body Temperature; Body Weight; Carrier Proteins; DNA; Enzyme-Linked Immunosorbent Assay; Fasting; Guanosine Diphosphate; Immunodiffusion; Ion Channels; Male; Membrane Proteins; Mice; Mitochondria; Mitochondrial Proteins; Oxygen Consumption; Proteins; Temperature; Uncoupling Protein 1