Altered hypothalamic function in response to glucose ingestion in obese humans

The hypothalamus plays a central role in the regulation of energy intake an d feeding behavior. However, the presence of a functional abnormality in th e hypothalamus in humans that may be related to excess energy intake and ob esity has yet to be demonstrated in vivo. We, therefore, used functional ma gnetic 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/m (2)) and 10 lean (32 +/- 4 years of age, BMI 22.0 +/- 0.9 kg/m(2)) 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 T-2*-weighted gradient-echo pulse sequence. After glucose inge stion, lean subjects demonstrated an inhibition of the fMRI signal in the a reas 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 ta ken to reach the maximum inhibitory response correlated with the fasting pl asma glucose (r = 0,75, P < 0.001) and insulin (r = 0,47, P < 0.05) concent rations 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.