In vivo fMRI demonstration of hypothalamic function following intraperitoneal glucose administration in a rat model.

The hypothalamic functional MRI (fMRI) response in an animal model was studied following energy intake. Six fasted (12 h) Sprague-Dawley (SD) rats were administered an intraperitoneal injection of glucose (0.72 grams/kg body weight), while a mid-sagittal slice through the hypothalamus was continuously imaged for 60 min using a conventional T2*-weighted gradient-echo sequence. All rats demonstrated a significant acute transient decrease in the fMRI signal intensity (mean: 3.4%) in the hypothalamic region within 12-16 min after intraperitoneal glucose injection. The SD rat may be a suitable model for future fMRI studies of the hypothalamus involving the administration of exogenous nutrients and medications.

Altered hypothalamic function in response to glucose ingestion in obese humans.

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.