Long-Term Persistence of Hormonal Adaptations to Weight Loss

Sumithran, Priya; Prendergast, Luke A.; Delbridge, Elizabeth; Purcell, Katrina; Shulkes, Arthur; Kriketos, Adamandia D.; Proietto, Joseph

doi:10.1056/nejmoa1105816

Cited by 1,168 publications

(778 citation statements)

References 36 publications

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“…These observations are particularly relevant, as while sustained calorie restriction has well-established effects on preventing cardiovascular disease and aging, 3,4 and confers cardioprotection to ischemia-reperfusion injury. 56 Clinical studies have repeatedly demonstrated an inability to maintain sustained calorie restriction for prolonged periods in obese subjects, 57,58 who are at markedly elevated risk for development of cardiovascular disease. Conversely, intermittent fasting is routinely practiced by diverse human social groups for religious and/or cultural reasons.…”

Section: Discussionmentioning

confidence: 99%

Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury

et al. 2015

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(2015) Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemiareperfusion injury, Autophagy, 11:9, 1537-1560, DOI: 10.1080/15548627.2015 Keywords: autophagy, fasting, ischemia-reperfusion, lysosome, myocardial infarctionAbbreviations: CMA, chaperone-mediated autophagy; CQ, chloroquine; GFP, green fluorescent protein; LAD, left anterior descending; LAMP2, lysosomal-associated membrane protein 2; MOI, multiplicity of infection; NRCMs, neonatal rat ventricular cardiac myocytes; q4D, quaque qutra die/every fourth day; qOD, quaque otra die/every other day; TFEB, transcription factor EB; MAP1LC3B (also abbreviated as LC3), microtubule-associated protein 1 light chain 3, isoform B; TTC, triphenyl tetrazolium chloride; LV, left ventricle; AAR, area at risk; WT, wild type.Autophagy, a lysosomal degradative pathway, is potently stimulated in the myocardium by fasting and is essential for maintaining cardiac function during prolonged starvation. We tested the hypothesis that intermittent fasting protects against myocardial ischemia-reperfusion injury via transcriptional stimulation of the autophagy-lysosome machinery. Adult C57BL/6 mice subjected to 24-h periods of fasting, every other day, for 6 wk were protected from invivo ischemia-reperfusion injury on a fed day, with marked reduction in infarct size in both sexes as compared with nonfasted controls. This protection was lost in mice heterozygous null for Lamp2 (coding for lysosomal-associated membrane protein 2), which demonstrate impaired autophagy in response to fasting with accumulation of autophagosomes and SQSTM1, an autophagy substrate, in the heart. In lamp2 null mice, intermittent fasting provoked progressive left ventricular dilation, systolic dysfunction and hypertrophy; worsening cardiomyocyte autophagosome accumulation and lack of protection to ischemia-reperfusion injury, suggesting that intact autophagy-lysosome machinery is essential for myocardial homeostasis during intermittent fasting and consequent ischemic cardioprotection. Fasting and refeeding cycles resulted in transcriptional induction followed by downregulation of autophagy-lysosome genes in the myocardium. This was coupled with fasting-induced nuclear translocation of TFEB (transcription factor EB), a master regulator of autophagy-lysosome machinery; followed by rapid decline in nuclear TFEB levels with refeeding. Endogenous TFEB was essential for attenuation of hypoxia-reoxygenation-induced cell death by repetitive starvation, in neonatal rat cardiomyocytes, in-vitro. Taken together, these data suggest that TFEBmediated transcriptional priming of the autophagy-lysosome machinery mediates the beneficial effects of fastinginduced autophagy in myocardial ischemia-reperfusion injury.

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Section: Discussionmentioning

confidence: 99%

Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury

et al. 2015

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“…Strong hormonal influences drive weight regain after weight loss 26 , and the individual variation in this process has yet to be characterised. However associations between success of initial weight loss and baseline leptin levels have been demonstrated 27 .…”

Section: Discussionmentioning

confidence: 99%

Baseline characteristics associated with different BMI trajectories in weight loss trials: a case for better targeting of interventions

2015

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Background/Objectives: Dietary weight loss interventions have heterogeneous outcomes in long-term studies, with many participants regaining part or all of the lost weight. Growth mixture modelling is a novel analytic approach that can be used to identify different trajectories of weight change during a trial rather than focussing on the total amount of weight lost. Subjects/Methods: Data were pooled from two 12-month dietary weight loss studies where no significant difference was detected between the treatment and control arms, thus allowing analysis independent of treatment. The data set included 231 subjects (74.5% female), with a mean weight loss of 6.40 kg (4.96). Growth mixture models were used to identify participants with similar trajectories of change in body mass index (BMI). Results: Three subgroups were identified. A rapid and continuing BMI loss over the study period (rapid, n=53), a rapid initial weight loss in the first 3 months with a slowing rate over the remaining 9 months (maintainers, n=146) and those with an initial loss trajectory, which slowed and began to increase at 9 months (recidivists, n=53). Age (s.d.) and BMI (s.d.) were significantly different between the three groups (rapid 53 years (7), 28.99 kg/m2 (3.30); maintainers 47 years (9), 30.90 kg/m2 (2.95); recidivists 44 years (7), 34.84 kg/m2 (1.92), both P<0.001). Conclusions: Older subjects with lower BMIs were more likely to have a rapid and continuing weight loss in a 1-year dietary-based weight loss intervention. Different interventional approaches may be necessary for different ages and baseline BMIs and stratification prior to randomisation may be necessary to prevent confounding in weight loss trials.

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“…Verdich et al demonstrated an attenuated postprandial GLP-1 response in obese subjects, which was significantly increased after a 6-month 15% diet-induced weight loss and appeared to be intermediate between the GLP-1 responses for obese and lean subjects, pointing toward a gradual normalization of GLP-1 responses with weight loss (7). However, other weight loss intervention studies have reported decreased (13,14,15) and unaltered (16) postprandial GLP-1 levels after a diet-induced weight loss.…”

Section: Introductionmentioning

confidence: 98%

“…The effect of weight loss on PYY 3-36 levels is, however, less clear, and both decreased (15) and unchanged (19) levels have been reported. Both fasting (20) and postprandial levels (21) increase after gastric bypass, and again, the effect seems to be larger after RYGB than after gastric banding.…”

Section: Introductionmentioning

confidence: 99%

Successful weight loss maintenance includes long-term increased meal responses of GLP-1 and PYY3–36

Iepsen

Lundgren

Holst

et al. 2016

European Journal of Endocrinology

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Objective: The hormones glucagon-like peptide 1 (GLP-1), peptide YY ), ghrelin, glucose-dependent insulinotropic polypeptide (GIP) and glucagon have all been implicated in the pathogenesis of obesity. However, it is unknown whether they exhibit adaptive changes with respect to postprandial secretion to a sustained weight loss. Design: The study was designed as a longitudinal prospective intervention study with data obtained at baseline, after 8 weeks of weight loss and 1 year after weight loss. Methods: Twenty healthy obese individuals obtained a 13% weight loss by adhering to an 8-week very low-calorie diet (800 kcal/day). After weight loss, participants entered a 52-week weight maintenance protocol. Plasma levels of GLP-1, PYY 3-36 , ghrelin, GIP and glucagon during a 600-kcal meal were measured before weight loss, after weight loss and after 1 year of weight maintenance. Area under the curve (AUC) was calculated as total AUC (tAUC) and incremental AUC (iAUC). Results: Weight loss was successfully maintained for 52 weeks. iAUC for GLP-1 increased by 44% after weight loss (P < 0.04) and increased to 72% at week 52 (P = 0.0001). iAUC for PYY 3-36 increased by 74% after weight loss (P<0.0001) and by 36% at week 52 (P = 0.02). tAUC for ghrelin increased by 23% after weight loss (P<0.0001), but at week 52, the increase was reduced to 16% compared with before weight loss (P = 0.005). iAUC for GIP increased by 36% after weight loss (P = 0.001), but returned to before weight loss levels at week 52. Glucagon levels were unaffected by weight loss. Conclusions: Meal responses of GLP-1 and PYY 3-36 remained increased 1 year after weight maintenance, whereas ghrelin and GIP reverted toward before-weight loss values. Thus, an increase in appetite inhibitory mechanisms and a partly decrease in appetite-stimulating mechanisms appear to contribute to successful long-term weight loss maintenance.

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Long-Term Persistence of Hormonal Adaptations to Weight Loss

Cited by 1,168 publications

References 36 publications

Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury

Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury

Baseline characteristics associated with different BMI trajectories in weight loss trials: a case for better targeting of interventions

Successful weight loss maintenance includes long-term increased meal responses of GLP-1 and PYY3–36

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