Dataset Information

The association between leptin and weight maintenance outcome in anorexia nervosa.

ABSTRACT:

Objective

Relapse after weight restoration in anorexia nervosa (AN) is a critical problem. Higher body fat percentage after weight gain has been shown to predict better weight maintenance outcome. Leptin, a fat-derived hormone, has been associated with progress during weight gain, but its association with weight maintenance is unknown. This study aims to determine whether leptin levels after weight restoration in AN are associated with weight maintenance.

Method

Participants were 41 women with AN hospitalized for inpatient treatment. Participants were evaluated 2-4 weeks after weight restoration to body mass index (BMI) ≥ 19.5 kg/m² for plasma leptin and body composition. Weight maintenance outcome was defined by whether a participant maintained a BMI of at least 18.5 kg/m² at the end of 1 year following hospital discharge.

Results

Twenty (48.8%) out of 41 patients maintained their weight at 1 year. Percent body fat and leptin were significantly higher in the group who maintained weight (body fat, p = .004, Hedges' g = 0.944; log-leptin, p = .010, Hedges' g = 0.821), but there were no differences in predischarge BMI, duration of illness, and duration of amenorrhea. Using regression modeling, only higher log-leptin (p_Wald = .021) and percent body fat (p_Wald = .010), as well as fat-adjusted leptin (p_Wald = .029), independently predicted weight maintenance at 1 year.

Discussions

Our findings suggest that for acutely-weight restored women with AN, higher predischarge leptin measurements are associated with better outcome in the year following treatment. Prospective studies examining leptin as well as other parameters of metabolic health could offer insights into biomarkers that may improve clinical outcomes.

SUBMITTER: Kim Y

PROVIDER: S-EPMC9851598 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Publications

The association between leptin and weight maintenance outcome in anorexia nervosa.

Kim Youngjung Y Hersch Jonathan J Bodell Lindsay P LP Schebendach Janet J Hildebrandt Tom T Walsh B Timothy BT Mayer Laurel E S LES

The International journal of eating disorders 20201113 4

<h4>Objective</h4>Relapse after weight restoration in anorexia nervosa (AN) is a critical problem. Higher body fat percentage after weight gain has been shown to predict better weight maintenance outcome. Leptin, a fat-derived hormone, has been associated with progress during weight gain, but its association with weight maintenance is unknown. This study aims to determine whether leptin levels after weight restoration in AN are associated with weight maintenance.<h4>Method</h4>Participants were ...[more]

PMID: 33185933

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Project description:Epigenetic alterations are increasingly implicated in the pathophysiology of anorexia nervosa (AN) but are as yet poorly understood. We investigated possible associations between the leptin gene (LEP) and the leptin receptor gene (LEPR) DNA promoter methylation and (1) a diagnosis of AN and (2) outcome after a 10 months psychotherapeutic outpatient treatment. 129 (LEPR: n = 135) patients with AN were investigated during the large scale psychotherapeutic Anorexia Nervosa Treatment Outpatient Study (ANTOP) trial, compared to 117 (LEPR: n = 119) age and height matched, normal-weight healthy controls. Blood samples were taken at baseline, the end of therapy (40 weeks) and the 12-months follow-up and compared to controls. Methylation was measured in whole blood via bisulfite sequencing. Within the promoter region 32 (LEP) and 39 CpG sites (LEPR) were analyzed. Two key findings were observed. First, LEP and LEPR methylation at baseline were lower in patients compared to controls (LEP: [%] AN: 30.94 ± 13.2 vs. controls: 34.53 ± 14.6); LEPR ([%] AN: 3.73 ± 5.4 vs. controls: 5.22 ± 8.3, mixed linear models: both P < 0.001). Second, lower DNA methylation of the LEP promoter, with a dynamic upregulation during treatment, was associated with a full recovery in AN patients (% change from baseline to follow-up in full recovery patients: +35.13% (SD: 47.56); mixed linear model: P < 0.0001). To test for potential predictive properties of mean LEP DNA methylation a LEP DNA methylation cut-off (31.25% DNA methylation) was calculated, which significantly discriminated full recovery vs. full syndrome AN patients. This cut-off was then tested in a group of previously unclassified patients (missing follow-up data of the Structured Interview for Anorexic and Bulimic disorders; n = 33). Patients below the cut-off (31.25% LEP DNA methylation) showed an increase in BMI over time, while those above the cut-off had a decrease in BMI (ANOVA at the 12-months follow-up: P = 0.0142). To our knowledge, this is the first study investigating epigenetic alterations in AN over time. Our findings indicate that LEP DNA methylation might be involved in the disease course of AN.

Project description:ImportanceIndividuals with anorexia nervosa maintain extremely low body weights despite elevations in the circulating orexigenic hormone ghrelin. Whether circulating levels of endogenous ghrelin are associated with weight gain in anorexia nervosa is unknown.ObjectiveTo examine the association between baseline ghrelin and future weight change in individuals with anorexia nervosa.Design, setting, and participantsThis prospective cohort study was conducted between April 1, 2014, and March 31, 2020, in the US. Girls and women aged 10 to 22 years were recruited from the greater Boston area from community and area treatment centers, enrolled, and followed up for 18 months. Statistical analyses were performed between January and August 2022.ExposuresPresence or absence of anorexia nervosa and elevations in endogenous ghrelin.Main outcomes and measuresChanges in age- and sex-standardized body mass index percentiles from baseline to 9- and 18-month follow-up were the main outcomes of interest.ResultsA total of 68 girls and young women (11 [16%] Asian, 4 [6%] Hispanic or Latina, 51 [75%] White [non-Hispanic or Latina], and 2 [3%] other race or ethnicity), including 35 with anorexia nervosa and 33 healthy controls of similar Tanner stage, were included in this study. Anorexia nervosa and healthy control groups were not statistically different by race and ethnicity, Tanner stage, number completing follow-up visits, and the duration between baseline and follow-up visits. At baseline, individuals with anorexia nervosa were slightly older (median [IQR], 20.1 [18.5-21.0] vs 18.7 [14.7-19.4] years; P = .005), had lower body mass index percentiles (median [IQR], 2.4 [0.3-4.7] vs 52.9 [40.4-68.3]; P < .001), and had elevated circulating ghrelin area under the curve composite index (median [IQR], 1389.4 [1082.5-1646.4] vs 958.5 [743.0-1234.5] pg/mL; P = .003) compared with healthy individuals. In linear mixed-effects regression analyses, baseline ghrelin was associated with prospective weight gain after adjusting for diagnosis, age, race, and duration of follow-up (odds ratio, 2.35; 95% CI, 1.43-3.73; P = .004).Conclusions and relevanceIn this cohort study, endogenous ghrelin was associated with longitudinal weight gain in individuals with anorexia nervosa. Further studies are warranted to confirm this result and examine its potential clinical utility in treatment development.

Project description:IntroductionDisruptions in homeostatic and hedonic food motivation are proposed to underlie anorexia nervosa (AN) and atypical AN, restrictive eating disorders which commonly onset in puberty. Ghrelin, a neuroprotective hormone that drives hedonic eating is increased in AN and is expressed in the hippocampus. White matter (WM) undergoes significant change during puberty in regions involved in food motivation, particularly WM tracts connected with the hippocampus. The association between ghrelin and WM region of interest (ROI) with hippocampal connections in restrictive eating disorders, particularly in adolescence during key neurodevelopmental growth, is unknown.MethodsWe evaluated fasting plasma ghrelin and WM microstructure (measured by free-water corrected fractional anisotropy (FA-t)) in WM ROIs with hippocampal connections - the fornix and the hippocampal portion of the cingulum - in 56 adolescent females (age range: 11.9 - 22.1 y; mean: 19.0 y) with low-weight eating disorders including AN and atypical AN (N = 36) and healthy controls (N = 20).ResultsFA-t in the fornix or hippocampal portion of the fornix did not differ between groups. Ghrelin was higher in AN/atypical AN vs. HC and was positively correlated with puberty stage in the AN/atypical AN group, but not the HC group. The correlation between ghrelin and FA-t in the fornix was significantly different in females with AN/atypical AN compared to controls. In AN/atypical AN, pubertal stage moderated the relation between fasting plasma ghrelin and FA-t in the fornix: higher fasting ghrelin was associated with lower FA-t in the fornix in late-post-puberty, but was not associated with FA-t in the early to mid stages of puberty.ConclusionsIn post-pubertal females with low-weight AN/atypical AN, higher levels of ghrelin are associated with lower FA-t in the fornix. This relationship is not evident in the early to mid stages of puberty in AN/atypical AN or in HC, and may reflect a lack of possible neuroprotective effects of ghrelin in late-post puberty only. Understanding the effects of ghrelin on WM microstructure longitudinally and following recovery from AN/Atypical AN and how this differs across pubertal stages will be an important next step. These findings could ultimately inform treatment staging and aid in diagnosis and detection of AN/atypical AN.

Dataset Information

The association between leptin and weight maintenance outcome in anorexia nervosa.

Objective

Method

Results

Discussions

Publications

The association between leptin and weight maintenance outcome in anorexia nervosa.

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