Altered hypothalamic function in response to glucose ingestion in obese humans

• Published in: Diabetes (New York, N.Y.) Vol. 48; no. 9; pp. 1801 - 1806
• Main Authors: MATSUDA, M, YIJUN LIU, MAHANKALI, S, YONGLIN PU, MAHANKALI, A, JANEY WANG, DEFRONZO, R. A, FOX, P. T, GAO, J.-H
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.09.1999
• Subjects: Adult; Biological and medical sciences; Case-Control Studies; Diabetes; Dietary Carbohydrates - pharmacology; Drinking Behavior - drug effects; Energy Metabolism - physiology; Feeding Behavior - physiology; Female; Glucose; Glucose - pharmacology; Homeostasis - physiology; Humans; Hypothalamus; Hypothalamus - pathology; Hypothalamus - physiology; Insulin; Linear Models; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Medical sciences; Metabolic diseases; Obesity; Obesity - physiopathology; Pathogenesis; Physiological aspects; Plasma; Human; Obesity; Metabolic disorder; Pathogenesis; Central nervous system; Hormonal regulation; Glucose; Hypothalamus; Nuclear magnetic resonance; Brain (vertebrata); Ingestion
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.48.9.1801

Altered hypothalamic function in response to glucose ingestion in obese humans. M Matsuda , Y Liu , S Mahankali , Y Pu , A Mahankali , J Wang , R A DeFronzo , P T Fox and J H Gao Department of Medicine, University of Texas Health Science Center, San Antonio 78284, USA. Abstract The hypothalamus plays a central role in the regulation of energy intake and feeding behavior. However, the presence of a functional abnormality in the hypothalamus in humans that may be related to excess energy intake and obesity has yet to be demonstrated in vivo. We, therefore, used functional magnetic resonance imaging (fMRI) to monitor hypothalamic function after oral glucose intake. The 10 obese (34 +/- 2 years of age, BMI 34.2 +/- 1.3 kg/m2) and 10 lean (32 +/- 4 years of age, BMI 22.0 +/- 0.9 kg/m2) subjects with normal glucose tolerance ingested 75 g of glucose while a midsagittal slice through the hypothalamus was continuously imaged for 50 min using a conventional T2*-weighted gradient-echo pulse sequence. After glucose ingestion, lean subjects demonstrated an inhibition of the fMRI signal in the areas corresponding to the paraventricular and ventromedial nuclei. In obese subjects, this inhibitory response was markedly attenuated (4.8 +/- 1.3 vs. 7.0 +/- 0.6% inhibition, P < 0.05) and delayed (9.4 +/- 0.5 vs. 6.4 +/- 0.5 min, P < 0.05) compared with that observed in lean subjects. The time taken to reach the maximum inhibitory response correlated with the fasting plasma glucose (r = 0.75, P < 0.001) and insulin (r = 0.47, P < 0.05) concentrations in both lean and obese subjects. These results demonstrate in vivo, for the first time, the existence of differential hypothalamic function in lean and obese humans that may be secondary to obesity.