Seydoux J, Chinet A, Schneider-Picard G, Bas S, Imesch E, Assimacopoulos-Jeannet F, Giacobino J P, Girardier L
Endocrinology. 1983 Aug;113(2):604-10. doi: 10.1210/endo-113-2-604.
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.
据报道，链脲佐菌素诱导的糖尿病大鼠存在饮食诱导性产热和耐寒性缺陷。由于棕色脂肪组织（BAT）是大鼠饮食和寒冷诱导性产热的主要效应器，因此通过比较链脲佐菌素诱导的糖尿病大鼠和对照大鼠在基础条件下以及神经刺激、去甲肾上腺素（NE）或添加辛酸激活期间的BAT代谢，研究了这些缺陷的可能原因。在大鼠肩胛间BAT（IBAT）中测量了以下代谢指标：1）组织组成，2）通过直接微量热法测量的产热率，3）通过反射光谱法测量的与酰基辅酶A脱氢酶途径相关的黄素蛋白的氧化还原状态，4）通过表面发射荧光测量的NAD(P)的氧化还原状态，以及5）IBAT匀浆中的脂肪酸激活和β-氧化活性。在链脲佐菌素诱导的糖尿病大鼠中，IBAT萎缩（DNA含量未改变，蛋白质和脂质含量降低）。基础和NE刺激后的总产热率分别下降了75%和56%。通过黄素蛋白氧化还原状态或酶法测量的脂肪酸β-氧化的比活性分别下降了52%和59%。NAD(P)的基础氧化还原水平比对照组高约3倍，与对照组织中观察到的还原相反，NE刺激导致氧化。这些结果表明，链脲佐菌素诱导的糖尿病大鼠的IBAT代谢能力降低，进一步表明β-氧化能力的降低显著导致了代谢改变。
