Impaired glucose-induced thermogenesis in skeletal muscle in obesity. The role of the sympathoadrenal system.
From a 7-day food recording in 29 morbidly obese patients two groups of six patients each were selected: a high-energy-intake group (HEI) and a low-energy-intake group (LEI). The groups were otherwise comparable. Five lean subjects served as controls for some observations. Oral glucose tolerance tests showed that all patients in the HEI group and the lean controls had normal glucose tolerance, whereas it was abnormal in all subjects in the LEI group. The fasting metabolic rate did not differ between the obese groups but was significantly lower in the lean group. The glucose-induced thermogenesis during 180 min expressed as a percentage of the energy content of the glucose load was lower in both obese groups compared with the lean controls (lean: +11.5 per cent, HEI: +5.3 per cent and LEI: -4.2 per cent, HEI vs lean: P = 0.04 and LEI vs lean: P = 0.005), and lower in the LEI group compared with the HEI group (P = 0.02). The integrated increase in leg oxygen consumption after glucose was also smaller in the LEI group than in the HEI group (15 +/- 269 vs 987 +/- 356 ml, P less than 0.05). The arterial noradrenaline response to glucose was significantly diminished in both obese groups compared with the lean controls. Glucose induced a similar increase in leg noradrenaline release in both obese groups, whereas the arterial adrenaline level was lower in the LEI group compared with the HEI group and with the lean controls (P = 0.04). Among the obese subjects the degree of glucose intolerance was inversely correlated with the post-glucose arterial adrenaline level (r = -0.55, and P = 0.04), and positively correlated with the fractional leg adrenaline extraction (r = 0.71, and P = 0.003). The results suggest that patients who are obese in spite of a fairly low energy intake have a reduced glucose-induced facultative thermogenesis, and that the defect is at least in part located in skeletal muscle. Since the sympathetic nervous system is partly responsible for the glucose-induced thermogenesis, the reduced thermogenic response in the obese patients may be due to an impaired activation of the sympathetic nervous system. It is hypothesized that the reduced arterial adrenaline level in the LEI group is caused by hyperglycaemic suppression of the adrenomedullary secretion and further that this may be a link connecting deterioration of glucose tolerance and a thermogenic defect in obesity.
D000311:Adrenal Glands / Q000503:physiopathology; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002395:Catecholamines / Q000097:blood; D002149:Energy Intake; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D005990:Glycerol / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007866:Leg / Q000098:blood supply; D008297:Male; D009132:Muscles / Q000378:metabolism*; D009767:Obesity, Morbid / Q000378:metabolism* / Q000503:physiopathology; D010101:Oxygen Consumption; D012039:Regional Blood Flow; D013564:Sympathetic Nervous System / Q000503:physiopathology; D013963:Thyroid Hormones / Q000097:blood
D001786:Blood Glucose; D002395:Catecholamines; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D013963:Thyroid Hormones; D005990:Glycerol