Brown adipose tissue metabolism in streptozotocin-diabetic rats.
Defects of both diet-induced thermogenesis and cold tolerance have been reported for streptozotocin-diabetic rats. Since brown adipose tissue (BAT) is a major effector of both diet- and cold-induced thermogenesis in the rat, the possible cause of these defects was investigated by comparing BAT metabolism under basal conditions and during activation by nerve stimulation, norepinephrine (NE), or octanoate addition in both streptozotocin-diabetic rats and in controls. The following metabolic indices were measured in rat interscapular BAT (IBAT): 1) tissue composition, 2) heat production rate as measured by direct microcalorimetry, 3) redox state of flavoproteins linked to the acyl-coenzyme A dehydrogenase pathway as measured by reflection spectrometry, 4) redox state of NAD(P) as measured by surface-emitted fluorescence, and 5) fatty acid activation and beta-oxidation activities in IBAT homogenate. In streptozotocin-diabetic rats, IBAT was atrophied (DNA content unmodified, protein and lipid content decreased). The basal and NE-stimulated total heat production rates showed a 75% and 56% decrease, respectively. The specific activity of fatty acid beta-oxidation as measured by flavoprotein redox state or enzymatically was decreased by 52% and 59%, respectively. The basal redox level of NAD(P) was about 3 times higher than in the controls and NE stimulation resulted in oxidation in contrast to the reduction observed in control tissues. These results show that the metabolic capacity of IBAT from streptozotocin-diabetic rats is decreased and further suggest that the reduced capacity for beta-oxidation contributes significantly to the metabolic alteration.
D002001:Adipose Tissue, Brown / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D003066:Coenzyme A Ligases / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004558:Electric Stimulation; D007700:Kinetics; D008297:Male; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D009243:NAD; D009249:NADP; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase