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:Background. Differential gene expression in adipose tissue during diet-induced weight loss followed by a weight stability period is not well characterized. Markers of these processes may provide a deeper understanding of the underlying mechanisms. Objective. To identify differentially expressed genes in human adipose tissue during weight loss and weight maintenance after weight loss. Design. RNA from subcutaneous abdominal adipose tissue from nine obese subjects was obtained and analyzed at baseline, after weight reduction on a low calorie diet (LCD), and after a period of group therapy in order to maintain weight stability. Results. Subjects lost 18.8 + 5.4% of their body weight during the LCD and maintained this weight during group therapy. Insulin sensitivity (HOMA) improved after weight loss with no further improvement during weight maintenance. Cyclin-dependent kinase inhibitor 2B (CDKN2B) and JAZF zinc finger 1 (JAZF1), associated with type 2 diabetes, were downregulated. We could also confirm the downregulation of candidates for obesity and related traits, such as tenomodulin (TNMD) and matrix metallopeptidase 9 (MMP9), with weight loss. The expression of other candidates, such as cell death-inducing DFFA-like effector A (CIDEA) and stearoyl-CoA desaturase (SCD) were upregulated during weight loss but returned to baseline levels during weight maintenance. Conclusion. Genes in the adipose tissue are differentially expressed during weight loss and weight maintenance after weight loss. Genes that show sustained regulation may be of potential interest as markers of the beneficial effects of weight loss whereas others seem to be primarily involved in the process of weight loss itself. Nine participants were prescribed a low calorie diet (LCD) containing 1200 kcal/day for approximately three months (101 ± 26 days). Following the weight reduction phase the participants attended a six month follow-up period (167 ± 37 days). By protocol design, subjects were eligible to enter the study if they had lost at least 10% of their initial body weight during the LCD-period and maintained this weight (+5%) after group therapy. Subcutaneous adipose tissue samples were obtained at three time-points: (i) at baseline, (ii) after weight reduction when subjects were no longer losing weight, and (iii) after the group therapy weight maintenance phase.

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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