Altered hypothalamic function in response to glucose ingestion in obese humans

Masafumi Matsuda, Yijun Liu, Srikanth Mahankali, Yonglin Pu, Archana Mahankali, Janey Wang, Ralph A. DeFronzo, Peter T. Fox, Jia Hong Gao

Research output: Contribution to journalArticlepeer-review

225 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1801-1806
Number of pages6
Issue number9
StatePublished - 1999

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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