Dataset Information

Effects of reduced weight maintenance and leptin repletion on functional connectivity of the hypothalamus in obese humans.

ABSTRACT: Treating obesity has proven to be an intractable challenge, in part, due to the difficulty of maintaining reduced weight. In our previous studies of in-patient obese subjects, we have shown that leptin repletion following a 10% or greater weight loss reduces many of the metabolic (decreased energy expenditure, sympathetic nervous system tone, and bioactive thyroid hormones) and behavioral (delayed satiation) changes that favor regain of lost weight. FMRI studies of these same subjects have shown leptin-sensitive increases in activation of the right hypothalamus and reduced activation of the cingulate, medial frontal and parahippocampal gryi, following weight loss, in response to food stimuli. In the present study, we expanded our cohort of in-patient subjects and employed psychophysiological interaction (PPI) analysis to examine changes in the functional connectivity of the right hypothalamus. During reduced-weight maintenance with placebo injections, the functional connectivity of the hypothalamus increased with visual areas and the dorsal anterior cingulate (dorsal ACC) in response to food cues, consistent with higher sensitivity to food. During reduced-weight maintenance with leptin injections, however, the functional connectivity of the right hypothalamus increased with the mid-insula and the central and parietal operculae, suggesting increased coupling with the interoceptive system, and decreased with the orbital frontal cortex, frontal pole and the dorsal ACC, suggesting a down-regulated sensitivity to food. These findings reveal neural mechanisms that may underlie observed changes in sensitivity to food cues in the obese population during reduced-weight maintenance and leptin repletion.

SUBMITTER: Hinkle W

PROVIDER: S-EPMC3605420 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Effects of reduced weight maintenance and leptin repletion on functional connectivity of the hypothalamus in obese humans.

Hinkle William W Cordell Michael M Leibel Rudy R Rosenbaum Michael M Hirsch Joy J

PloS one 20130321 3

Treating obesity has proven to be an intractable challenge, in part, due to the difficulty of maintaining reduced weight. In our previous studies of in-patient obese subjects, we have shown that leptin repletion following a 10% or greater weight loss reduces many of the metabolic (decreased energy expenditure, sympathetic nervous system tone, and bioactive thyroid hormones) and behavioral (delayed satiation) changes that favor regain of lost weight. FMRI studies of these same subjects have shown ...[more]

PMID: 23555620

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Project description:Introductionfunctional and structural MRI studies suggest that the orexin (hypocretin) deficiency in the dorso-lateral hypothalamus of narcoleptic patients would influence both brain metabolism and perfusion and would cause reduction in cortical grey matter. Previous fMRI studies have mainly focused on cerebral functioning during emotional processing. The aim of the present study was to explore the hemodynamic behaviour of spontaneous BOLD fluctuation at rest in patients with Narcolepsy type 1 (NT1) close to disease onset.MethodsFifteen drug naïve children/adolescents with NT1 (9 males; mean age 11.7 ± 3 years) and fifteen healthy children/adolescents (9 males; mean age 12.4 ± 2.8 years) participated in an EEG-fMRI study in order to investigate the resting-state functional connectivity of hypothalamus and amygdala. Functional images were acquired on a 3 T system. Seed-based functional connectivity analyses were performed using SPM12. Regions of Interest were the lateral hypothalamus and the amygdala.Resultscompared to controls, NT1 patients showed decreased functional connectivity between the lateral hypothalamus and the left superior parietal lobule, the hippocampus and the parahippocampal gyrus. Decreased functional connectivity was detected between the amygdala and the post-central gyrus and several occipital regions, whereas it was increased between the amygdala and the inferior frontal gyrus, claustrum, insula, and putamen.Conclusionin NT1 patients the abnormal connectivity between the hypothalamus and brain regions involved in memory consolidation during sleep, such as the hippocampus, may be linked to the loss of orexin containing neurons in the dorsolateral hypothalamus. Moreover, also functional connectivity of the amygdala seems to be influenced by the loss of orexin-containing neurons. Therefore, we can hypothesize that dysfunctional interactions between regions subserving the maintenance of arousal, memory and emotional processing may contribute to the main symptom of narcolepsy.

Dataset Information

Effects of reduced weight maintenance and leptin repletion on functional connectivity of the hypothalamus in obese humans.

Publications

Effects of reduced weight maintenance and leptin repletion on functional connectivity of the hypothalamus in obese humans.

Similar Datasets

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