Dataset Information

Evidence for a Non-leptin System that Defends against Weight Gain in Overfeeding.

ABSTRACT: Weight is defended so that increases or decreases in body mass elicit responses that favor restoration of one's previous weight. While much is known about the signals that respond to weight loss and the central role that leptin plays, the lack of experimental systems studying the overfed state has meant little is known about pathways defending against weight gain. We developed a system to study this physiology and found that overfed mice defend against increased weight gain with graded anorexia but, unlike weight loss, this response is independent of circulating leptin concentration. In overfed mice that are unresponsive to orexigenic stimuli, adipose tissue is transcriptionally and immunologically distinct from fat of ad libitum-fed obese animals. These findings provide evidence that overfeeding-induced obesity alters adipose tissue and central responses in ways that are distinct from ad libitum obesity and activates a non-leptin system to defend against weight gain.

SUBMITTER: Ravussin Y

PROVIDER: S-EPMC6082718 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Evidence for a Non-leptin System that Defends against Weight Gain in Overfeeding.

Ravussin Yann Y Edwin Ethan E Gallop Molly M Xu Lumei L Bartolomé Alberto A Kraakman Michael J MJ LeDuc Charles A CA Ferrante Anthony W AW

Cell metabolism 20180621 2

Weight is defended so that increases or decreases in body mass elicit responses that favor restoration of one's previous weight. While much is known about the signals that respond to weight loss and the central role that leptin plays, the lack of experimental systems studying the overfed state has meant little is known about pathways defending against weight gain. We developed a system to study this physiology and found that overfed mice defend against increased weight gain with graded anorexia ...[more]

PMID: 29937378

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Project description:BackgroundGreater increase in 24-h energy expenditure (24EE) during overfeeding and smaller decrease in 24EE during fasting ("spendthrift" metabolic phenotype) are associated with more weight loss during sustained caloric restriction in overweight subjects.ObjectivesThe aim of this study was to investigate whether these acute metabolic responses can also predict weight gain during sustained overfeeding in lean individuals.MethodsSeven lean men participated in this study. Prior to overfeeding, 24EE responses to fasting and 200% normal-protein overfeeding were measured in a whole-room indirect calorimeter. Volunteers underwent 6 wk of 150% low-protein (2%) overfeeding followed by another wk of weight-maintaining diet, during which 24EE was revaluated. Body composition, 24EE, and various hormone concentrations, including fibroblast growth factor 21 (FGF21), were assessed at baseline, at wk 1, 3, and 6 of the overfeeding period, and 1 wk following overfeeding through the use of dual-energy X-ray absorptiometry, indirect calorimetry, and ELISA. Cumulative energy surplus was calculated from 24EE, daily physical activity, and direct measurements of calories of nutrient intake, feces, and urine by bomb calorimetry.ResultsThe average weight gain during 6 wk of low-protein overfeeding was 3.8 kg (6.1%, min: +2.5%, max: +8.0%). During 24-h fasting at baseline, 24EE decreased on average (mean ± SD) by 158 ± 81 kcal/d (P = 0.007). Subjects with less 24EE decrease during fasting (more metabolically spendthrift individuals) gained less weight (r = -0.84, P = 0.03), less fat mass (r = -0.81, P = 0.049), and stored less calories (r = -0.91, P = 0.03) during overfeeding. Following overfeeding, increased 24EE above requirements for achieved body size was associated with less weight and fat mass gain (r = -0.78, P = 0.04) and with the increase in 24EE during 200% normal-protein overfeeding measured at baseline (r = 0.91, P = 0.005). Serum FGF21 concentrations increased up to 44-fold during overfeeding (P < 0.0001).ConclusionsLow-protein overfeeding may be an important tool to identify metabolic phenotypes (spendthrift compared with thrifty) that characterize susceptibility to weight gain. This trial was registered at clinicaltrials.gov as NCT00687115.

Dataset Information

Evidence for a Non-leptin System that Defends against Weight Gain in Overfeeding.

Publications

Evidence for a Non-leptin System that Defends against Weight Gain in Overfeeding.

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