Specific decrease of mitochondrial thermogenic capacity in brown adipose tissue of obese SHR/N-cp rats.
The metabolic properties of brown adipose tissue (BAT), liver, and skeletal muscles were compared in lean and obese diabetic SHR/N-cp rats (a new model of type II diabetes) to test whether the severe insulin resistance of obese animals is specifically associated with a thermogenic defect in BAT. The respiratory response of brown adipocytes to norepinephrine and to agents bypassing the adenylate cyclase complex (dibutyryl cyclic AMP and palmitate) was decreased by two-thirds in obese rats, thereby indicating the presence of a major postreceptor defect. Significantly, total BAT cytochrome oxidase activity, uncoupling protein content, and mitochondrial guanosine 5'-diphosphate binding (3 indexes of BAT thermogenic capacity) were also decreased by two-thirds. The specific activities of these parameters expressed per total BAT mitochondrial protein were not altered either. This indicates that the total number of mitochondria per cell is decreased in BAT of obese rats. In contrast, total tissue cytochrome oxidase activity, protein content, and DNA content all increased by two to three times in the liver of obese SHR/N-cp rats, but these parameters remained unchanged in skeletal muscles (vastus lateralis and soleus). Such a remarkable liver hypertrophy may have occurred as a consequence of the persistent hyperphagia-hyperinsulinemia of obese rats that induced a hyperplasia and/or a hepatocyte polyploidization. This observation together with the fact that daily energy expenditure associated with food intake was markedly increased in obese rats (representing as much as 25% of the total energy expenditure) strongly suggests that the liver plays a major role in energy balance in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Atgié
C
C
Department of Physiology, Laval University Medical School, Quebec, Canada.
Marette
A
A
Desautels
M
M
Tulp
O
O
Bukowiecki
L J
LJ
D002001:Adipose Tissue, Brown / Q000378:metabolism / Q000502:physiology / Q000503:physiopathology*; D000818:Animals; D001833:Body Temperature Regulation; D003994:Bucladesine / Q000494:pharmacology; D003433:Crosses, Genetic; D004247:DNA / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D006153:Guanosine Diphosphate / Q000378:metabolism; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000201:enzymology; D008931:Mitochondria, Muscle / Q000201:enzymology; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000503:physiopathology*; D009928:Organ Specificity; D010101:Oxygen Consumption / Q000187:drug effects; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011922:Rats, Mutant Strains / Q000502:physiology*; D013851:Thinness
D010169:Palmitic Acids; D006153:Guanosine Diphosphate; D019308:Palmitic Acid; D003994:Bucladesine; D004247:DNA; D003576:Electron Transport Complex IV; D009638:Norepinephrine