scholarly journals Biology's response to dieting: the impetus for weight regain

2011 ◽  
Vol 301 (3) ◽  
pp. R581-R600 ◽  
Author(s):  
Paul S. MacLean ◽  
Audrey Bergouignan ◽  
Marc-Andre Cornier ◽  
Matthew R. Jackman
Keyword(s):  
Weight Loss ◽  
Weight Reduction ◽  
Weight Regain ◽  
Energy Homeostasis ◽  
Biological Response ◽  
Recidivism Rate ◽  
Obese People ◽  
Low Fat Diet ◽  
Adiposity Signals

Dieting is the most common approach to losing weight for the majority of obese and overweight individuals. Restricting intake leads to weight loss in the short term, but, by itself, dieting has a relatively poor success rate for long-term weight reduction. Most obese people eventually regain the weight they have worked so hard to lose. Weight regain has emerged as one of the most significant obstacles for obesity therapeutics, undoubtedly perpetuating the epidemic of excess weight that now affects more than 60% of U.S. adults. In this review, we summarize the evidence of biology's role in the problem of weight regain. Biology's impact is first placed in context with other pressures known to affect body weight. Then, the biological adaptations to an energy-restricted, low-fat diet that are known to occur in the overweight and obese are reviewed, and an integrative picture of energy homeostasis after long-term weight reduction and during weight regain is presented. Finally, a novel model is proposed to explain the persistence of the “energy depletion” signal during the dynamic metabolic state of weight regain, when traditional adiposity signals no longer reflect stored energy in the periphery. The preponderance of evidence would suggest that the biological response to weight loss involves comprehensive, persistent, and redundant adaptations in energy homeostasis and that these adaptations underlie the high recidivism rate in obesity therapeutics. To be successful in the long term, our strategies for preventing weight regain may need to be just as comprehensive, persistent, and redundant, as the biological adaptations they are attempting to counter.

Peripheral metabolic responses to prolonged weight reduction that promote rapid, efficient regain in obesity-prone rats

2006 ◽  
Vol 290 (6) ◽  
pp. R1577-R1588 ◽  
Author(s):  
Paul S. MacLean ◽  
Janine A. Higgins ◽  
Matthew R. Jackman ◽  
Ginger C. Johnson ◽  
Brooke K. Fleming-Elder ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Weight Reduction ◽  
Weight Regain ◽  
Energy Gap ◽  
Neural Pathways ◽  
Low Fat ◽  
Cross Sectional ◽  
Low Fat Diet

Weight regain after weight loss is the most significant impediment to long-term weight reduction. We have developed a rodent paradigm that models the process of regain after weight loss, and we have employed both prospective and cross-sectional analyses to characterize the compensatory adaptations to weight reduction that may contribute to the propensity to regain lost weight. Obese rats were fed an energy-restricted (50–60% kcal) low-fat diet that reduced body weight by 14%. This reduced weight was maintained for up to 16 wk with limited provisions of the low-fat diet. Intake restriction was then removed, and the rats were followed for 56 days as they relapsed to the obese state. Prolonged weight reduction was accompanied by 1) a persistent energy gap resulting from an increased drive to eat and a reduced expenditure of energy, 2) a higher caloric efficiency of regain that may be linked with suppressed lipid utilization early in the relapse process, 3) preferential lipid accumulation in adipose tissue accompanied by adipocyte hyperplasia, and 4) humoral adiposity signals that underestimate the level of peripheral adiposity and likely influence the neural pathways controlling energy balance. Taken together, long-term weight reduction in this rodent paradigm is accompanied by a number of interrelated compensatory adjustments in the periphery that work together to promote rapid and efficient weight regain. These metabolic adjustments to weight reduction are discussed in the context of a homeostatic feedback system that controls body weight.

scholarly journals Improvements in Long-Term Appetite-Regulating Hormones in Response to a Combined Lifestyle Intervention for Obesity

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A489-A490
Author(s):  
Susanne Kuckuck
Keyword(s):  
Weight Loss ◽  
Lifestyle Intervention ◽  
Weight Regain ◽  
Initial Weight ◽  
Short Term ◽  
Initial Weight Loss ◽  
Hormone Levels ◽  
Adiposity Signals ◽  
Term Energy

Abstract Altered levels of hormonal appetite regulators have been observed in obesity (BMI ≥ 30.0 kg/m2), most prominently increases of insulin and leptin (indicating resistance) as well as decreases of adiponectin - all of which are long-term energy regulators and adiposity signals. Disrupted signaling of these hormones may have detrimental effects on metabolism, but may also promote weight gain. Weight loss is often accompanied by normalizations of long-term adiposity signals, but findings concerning short-term appetite regulators after weight loss vary across interventions (e.g. very low calorie diets vs. exercise). Moreover, it is debated whether such weight-loss-induced hormonal changes may reflect a disposition for weight regain. Here, we investigated changes of long- and short-term appetite signals in response to an intensive 75-week combined lifestyle intervention (CLI) comprising a normocaloric healthy diet, physical activity and psychotherapy to promote improved long-term weight management. For 39 patients, data on fasting serum levels of appetite-regulating hormones (leptin, insulin, adiponectin, GIP, PP, PYY, CCK, FGF21) were available. Hormone levels were correlated to BMI at baseline (T0) and compared across three time points: T0, T1 (after 10 weeks; initial weight loss) and T2 (after 75 weeks; weight loss maintenance). T0-T1 hormone changes were correlated to BMI changes between T1 and T2 to investigate whether hormonal alterations during initial weight loss are associated with weight regain. At T0, hormone levels were not associated with BMI. BMI decreased significantly from T0 (40.13 kg/m2 ± 5.7) to T1 (38.2 ± 5.4, p < .001) which was maintained at T2 (38.2 kg/m2 ± 5.9, p < .001). There were no significant changes in GIP, PP, PYY, CCK and FGF21. Leptin decreased from T0 (44.9 ng/nl ± 15.3) to T1 (33 ng/nl ± 14.8, p < .001) and T2 (38.6 ng/nl ± 16.0, p < .01), just like insulin which was significantly decreased at T1 (123 pmol/l ± 65, p < .05) and T2 (128 pmol/l ± 64, p < .05) compared to T0 (160 pmol/l ± 80). Adiponectin did not change between T0 (3.36 ug/ml ± 2.1) and T1 (3.2 ug/ml ± 2.1), but was increased at T2 (3.7 ug/ml ± 2.9, p < .01) compared to T1. T0-T2 BMI decrease correlated positively with T0-T2 decreases in leptin (r = .667, p < .001), insulin (rho = .535, p < .001) and increases of adiponectin (r = .412, p < .01), but no other hormone. T0-T1 hormone changes did not predict T1-T2 BMI changes. Thus, a 75-week CLI was associated with beneficial changes in the long-term energy regulators adiponectin, leptin and insulin, but no changes in short-term appetite-regulating hormones were observed despite significant weight loss. Initial changes in appetite-regulating hormones were not associated with subsequent weight regain. Overall, our data suggest that a CLI does not lead to adverse changes in appetite regulation, but rather long-term improvements such as e.g. increased leptin and insulin sensitivity.

scholarly journals Long-term effects of a very-low-carbohydrate weight loss diet compared with an isocaloric low-fat diet after 12 mo

2009 ◽  
Vol 90 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Grant D Brinkworth ◽  
Manny Noakes ◽  
Jonathan D Buckley ◽  
Jennifer B Keogh ◽  
Peter M Clifton
Keyword(s):  
Weight Loss ◽  
Long Term Effects ◽  
Low Fat ◽  
Weight Loss Diet ◽  
Low Fat Diet ◽  
Low Carbohydrate

scholarly journals The effect of rate of weight loss on long-term weight regain in adults with overweight and obesity

Obesity ◽  
2016 ◽  
Vol 24 (2) ◽  
pp. 321-327 ◽  
Author(s):  
Roel G. Vink ◽  
Nadia J. T. Roumans ◽  
Laura A. J. Arkenbosch ◽  
Edwin C. M. Mariman ◽  
Marleen A. van Baak
Keyword(s):  
Weight Loss ◽  
Weight Regain ◽  
Overweight And Obesity

scholarly journals Lipoprotein Lipase Overexpression in Skeletal Muscle Attenuates Weight Regain by Potentiating Energy Expenditure

2021 ◽  
Author(s):  
Ada Admin ◽  
David M Presby ◽  
Michael C Rudolph ◽  
Vanessa D Sherk ◽  
Matthew R Jackman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Energy Expenditure ◽  
Lipoprotein Lipase ◽  
Weight Regain ◽  
Energy Homeostasis ◽  
Fat Metabolism ◽  
Fat Oxidation ◽  
Oxidative Capacity ◽  
Expression Of Genes

Moderate weight loss improves numerous risk factors for cardiometabolic disease; however, long-term weight loss maintenance (WLM) is often thwarted by metabolic adaptations that suppress energy expenditure and facilitate weight regain. Skeletal muscle has a prominent role in energy homeostasis; therefore, we investigated the effect of WLM and weight regain on skeletal muscle in rodents. In skeletal muscle of obesity-prone rats, WLM reduced fat oxidative capacity and downregulated genes involved in fat metabolism. Interestingly, even after weight was regained, genes involved in fat metabolism genes were also reduced. We then subjected mice with skeletal muscle lipoprotein lipase overexpression (mCK-hLPL), which augments fat metabolism, to WLM and weight regain and found that mCK-hLPL attenuates weight regain by potentiating energy expenditure. Irrespective of genotype, weight regain suppressed dietary fat oxidation and downregulated genes involved in fat metabolism in skeletal muscle. However, mCK-hLPL mice oxidized more fat throughout weight regain and had greater expression of genes involved in fat metabolism and lower expression of genes involved in carbohydrate metabolism during WLM and regain. In summary, these results suggest that skeletal muscle fat oxidation is reduced during WLM and regain, and therapies that improve skeletal muscle fat metabolism may attenuate rapid weight regain.

scholarly journals Bariatric surgery, lifestyle interventions and orlistat for severe obesity: the REBALANCE mixed-methods systematic review and economic evaluation

2018 ◽  
Vol 22 (68) ◽  
pp. 1-246 ◽  
Author(s):  
Alison Avenell ◽  
Clare Robertson ◽  
Zoë Skea ◽  
Elisabet Jacobsen ◽  
Dwayne Boyers ◽  
...  
Keyword(s):  
Weight Loss ◽  
Cost Effectiveness ◽  
Weight Regain ◽  
Severe Obesity ◽  
Clinical Effectiveness ◽  
Cost Effective ◽  
Research Unit ◽  
Look Ahead ◽  
Obesity Trends

Background Adults with severe obesity [body mass index (BMI) of ≥ 35 kg/m2] have an increased risk of comorbidities and psychological, social and economic consequences. Objectives Systematically review bariatric surgery, weight-management programmes (WMPs) and orlistat pharmacotherapy for adults with severe obesity, and evaluate the feasibility, acceptability, clinical effectiveness and cost-effectiveness of treatment. Data sources Electronic databases including MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials and the NHS Economic Evaluation Database were searched (last searched in May 2017). Review methods Four systematic reviews evaluated clinical effectiveness, cost-effectiveness and qualitative evidence for adults with a BMI of ≥ 35 kg/m2. Data from meta-analyses populated a microsimulation model predicting costs, outcomes and cost-effectiveness of Roux-en-Y gastric bypass (RYGB) surgery and the most effective lifestyle WMPs over a 30-year time horizon from a NHS perspective, compared with current UK population obesity trends. Interventions were cost-effective if the additional cost of achieving a quality-adjusted life-year is < £20,000–30,000. Results A total of 131 randomised controlled trials (RCTs), 26 UK studies, 33 qualitative studies and 46 cost-effectiveness studies were included. From RCTs, RYGB produced the greatest long-term weight change [–20.23 kg, 95% confidence interval (CI) –23.75 to –16.71 kg, at 60 months]. WMPs with very low-calorie diets (VLCDs) produced the greatest weight loss at 12 months compared with no WMPs. Adding a VLCD to a WMP gave an additional mean weight change of –4.41 kg (95% CI –5.93 to –2.88 kg) at 12 months. The intensive Look AHEAD WMP produced mean long-term weight loss of 6% in people with type 2 diabetes mellitus (at a median of 9.6 years). The microsimulation model found that WMPs were generally cost-effective compared with population obesity trends. Long-term WMP weight regain was very uncertain, apart from Look AHEAD. The addition of a VLCD to a WMP was not cost-effective compared with a WMP alone. RYGB was cost-effective compared with no surgery and WMPs, but the model did not replicate long-term cost savings found in previous studies. Qualitative data suggested that participants could be attracted to take part in WMPs through endorsement by their health-care provider or through perceiving innovative activities, with WMPs being delivered to groups. Features improving long-term weight loss included having group support, additional behavioural support, a physical activity programme to attend, a prescribed calorie diet or a calorie deficit. Limitations Reviewed studies often lacked generalisability to UK settings in terms of participants and resources for implementation, and usually lacked long-term follow-up (particularly for complications for surgery), leading to unrealistic weight regain assumptions. The views of potential and actual users of services were rarely reported to contribute to service design. This study may have failed to identify unpublished UK evaluations. Dual, blinded numerical data extraction was not undertaken. Conclusions Roux-en-Y gastric bypass was costly to deliver, but it was the most cost-effective intervention. Adding a VLCD to a WMP was not cost-effective compared with a WMP alone. Most WMPs were cost-effective compared with current population obesity trends. Future work Improved reporting of WMPs is needed to allow replication, translation and further research. Qualitative research is needed with adults who are potential users of, or who fail to engage with or drop out from, WMPs. RCTs and economic evaluations in UK settings (e.g. Tier 3, commercial programmes or primary care) should evaluate VLCDs with long-term follow-up (≥ 5 years). Decision models should incorporate relevant costs, disease states and evidence-based weight regain assumptions. Study registration This study is registered as PROSPERO CRD42016040190. Funding The National Institute for Health Research Health Technology Assessment programme. The Health Services Research Unit and Health Economics Research Unit are core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate.

scholarly journals MON-LB101 5-Year Data of an Aggressive Pharmacological Approach to Moderate and Morbid Obesity: Is Prevention of Bariatric Surgery Feasible in the Long Run?

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Flavio Cadegiani
Keyword(s):  
Bariatric Surgery ◽  
Morbid Obesity ◽  
Weight Loss ◽  
Body Weight ◽  
Weight Regain ◽  
Morbidly Obese ◽  
Biochemical Profile ◽  
Initial Weight ◽  
Initial Weight Loss

Abstract Background: Maintenance of weight loss in patients that undergo weight loss interventions is highly challenging, irrespective of the type of approach to obesity (whether surgical, pharmacological, or non-pharmacological). We proposed a protocol of an aggressive clinical treatment for obesity aiming to prevent the need of bariatric surgery, in patients unwilling to undergo this procedure, by proposing a protocol that included the combination of different anti-obesity medications and non-pharmacological modalities, for longer duration, and with an active approach to prevent weight regain. Our initial 2-year data showed that 93% (40 of 43 patients) with moderate and morbid obesity were able to avoid the need of bariatric surgery, with concomitant improvements of the biochemical profile. However, whether these patients would maintain their successful rates after five years was uncertain. Our objective is to describe the efficacy and safety of a long term (5-year data) pharmacological and multi-modal treatment for moderate and severe obesity. Methods: The 40 patients that were successful in the two-year approach in our obesity center (Corpometria Institute, Brasilia, DF, Brazil) were enrolled. A long-term anti-obesity protocol was employed, with continuous or intermittent use of anti-obesity drugs, trimestral body composition analysis, psychotherapy, visit to a nutritionist every four months, and both resistance and endurance exercises at least four times a week. Body weight (BW), total weight excess (TWE), body fat, markers of lipid and glucose metabolism, liver function, and inflammation were analyzed. Subjects that dropped out were considered as weight regain. Therapeutic success for the 5-year follow-up included as the maintenance of &gt;20% loss of the initial BW loss, and no weight regain (or &lt; 20% of the initial weight loss). Results: A total of 27 patients (67.5%) were able to maintain the body weight, seven dropped out, and six regained more than 20% of the initial weight loss. Of these, 21 (77.8%) had significant further increase of muscle mass and decrease of fat loss, while 17 (63.0%) had further weight loss (p &lt; 0.05), compared to the 2-year data. Improvements on the biochemical profile persisted in all 27 patients, and had significant further improvements in 24 (88.9%) of these patients. Conclusion: The risk of weight regain five years after a weight loss treatment for obesity was significantly lower compared to previous literature, and comparable to the long-term outcomes of bariatric procedures. An aggressive, structured, and long-term clinical weight loss approach has been shown to be feasible, even for morbidly obese patients.

scholarly journals Hypothalamic γ-melanocyte stimulating hormone gene delivery reduces fat mass in male mice

2018 ◽  
Vol 239 (1) ◽  
pp. 19-31 ◽  
Author(s):  
K Eerola ◽  
S Virtanen ◽  
L Vähätalo ◽  
L Ailanen ◽  
M Cai ◽  
...  
Keyword(s):  
Weight Loss ◽  
Energy Balance ◽  
Gene Delivery ◽  
Fat Mass ◽  
Energy Homeostasis ◽  
Western Diet ◽  
Dependent Manner ◽  
Melanocyte Stimulating Hormone ◽  
Stimulating Hormone

γ-Melanocyte stimulating hormone (γ-MSH) is an endogenous agonist of the melanocortin 3-receptor (MC3R). Genetic disruption of MC3Rs increases adiposity and blunts responses to fasting, suggesting that increased MC3R signaling could be physiologically beneficial in the long term. Interestingly, several studies have concluded that activation of MC3Rs is orexigenic in the short term. Therefore, we aimed to examine the short- and long-term effects of γ-MSH in the hypothalamic arcuate nucleus (ARC) on energy homeostasis and hypothesized that the effect of MC3R agonism is dependent on the state of energy balance and nutrition. Lentiviral gene delivery was used to induce a continuous expression of γ-Msh only in the ARC of male C57Bl/6N mice. Parameters of body energy homeostasis were monitored as food was changed from chow (6 weeks) to Western diet (13 weeks) and back to chow (7 weeks). The γ-MSH treatment decreased the fat mass to lean mass ratio on chow, but the effect was attenuated on Western diet. After the switch back to chow, an enhanced loss in weight (−15% vs −6%) and fat mass (−37% vs −12%) and reduced cumulative food intake were observed in γ-MSH-treated animals. Fasting-induced feeding was increased on chow diet only; however, voluntary running wheel activity on Western diet was increased. The γ-MSH treatment also modulated the expression of key neuropeptides in the ARC favoring weight loss. We have shown that a chronic treatment intended to target ARC MC3Rs modulates energy balance in nutritional state-dependent manner. Enhancement of diet-induced weight loss could be beneficial in treatment of obesity.

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