Experimental demonstration of human weight homeostasis: implications for understanding obesity

The existence of a set-point for homeostatic control of human body weight is uncertain. To investigate its existence, technically difficult determinations of energy expenditure must be performed: this has resulted in contradictory reports. The present study was performed with new methods in two stages (77 and 133d respectively). Two healthy male subjects with rigorously controlled physical activity ingested three standardized diets of processed foods from the same manufacturer. Hypo-, iso- and hyperenergetic diets containing 6255kJ (1494kcal), 10073kJ (2406kcal) and 13791kJ (3294kcal) respectively were ingested during alternate periods; changes in body weight were measured. A new index of energy expenditure was calculated as the amount of weight lost in an 8h overnight period (WL8H). A digital scale was used in stage 1 and a mechanical scale in stage 2. The change in body weight in response to the isoenergetic diet differed according to the circumstances. In basal conditions, it was associated with weight stability. After weight loss from energy restriction, the isoenergetic diet led to weight gain. After weight gain from overeating, it led to weight loss. Diets of higher energy content were associated with greater WL8H (F>20; P<0·0001 for both subjects). Measurement variability was lower using a mechanical scale. The present study demonstrates the existence of a homeostatic control of human weight and describes a new index of energy expenditure measured in weight units. It also demonstrates that strict dietary supervision for months is possible. Investigation of the human body weight set-point is vital in understanding obesity.

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How strongly does appetite counter weight loss? Quantification of the homeostatic control of human energy intake

10.1101/051045 ◽

2016 ◽

Author(s):

David Polidori ◽

Arjun Sanghvi ◽

Randy Seeley ◽

Kevin D. Hall

Keyword(s):

Weight Loss ◽

Body Weight ◽

Feedback Control ◽

Energy Expenditure ◽

Energy Intake ◽

List Type ◽

Homeostatic Control ◽

Free Living ◽

Human Energy

AbstractObjectiveTo quantify the homeostatic feedback control of energy intake in response to long-term covert manipulation of energy balance in free-living humans.MethodsWe used a validated mathematical method to calculate energy intake changes during a 52 week placebo-controlled trial in 153 patients treated with canagliflozin, a sodium glucose co-transporter inhibitor that increases urinary glucose excretion thereby resulting in weight loss without patients being directly aware of the energy deficit. We analyzed the relationship between the body weight time course and the calculated energy intake changes using principles from engineering control theory. ResultsWe discovered that weight loss leads to a proportional homeostatic drive to increase energy intake above baseline by ~100 kcal/day per kg of lost weight – an amount more than 3-fold larger than the corresponding energy expenditure adaptations.ConclusionsWhile energy expenditure adaptations are often thought to be the main reason for slowing of weight loss and subsequent regain, feedback control of energy intake plays an even larger role and helps explain why long-term maintenance of a reduced body weight is so difficult.FundingThis research was supported by the Intramural Research Program of the NIH, National Institute of Diabetes & Digestive & Kidney Diseases, using data from a study sponsored by Janssen Research & Development, LLC.DisclosureD.P. is a full-time employee of Janssen Research & Development, LLC. K.D.H. reports patent pending on a method of personalized dynamic feedback control of body weight (US Patent Application No. 13/754,058; assigned to the NIH) and has received funding from the Nutrition Science Initiative to investigate the effects of ketogenic diets on human energy expenditure. R.S. is a paid consultant for Janssen, Novo Nordisk, Takeda, Daichii Sankyo, Novartis, Pfizer, Nestle, Circuit Therapeutics and Ethicon. R.S., also has received research support from Novo Nordisk, Ethicon, Sanofiand Boehringer Ingelheim. A.S. reports no conflicts of interest.What is already known about this subject?Human body weight is believed to be regulated by homeostatic feedback control of both energy intake and energy expenditure.Adaptations of energy expenditure to weight loss have been well-established, but the homeostatic control of energy intake has yet to be quantified.What this study addsWe provide the first quantification of the homeostatic control of energy intake in free-living humans.The increase in energy intake per kg of weight lost is several-fold larger than the known energy expenditure adaptations.Homeostatic control of energy intake is likely the primary reason why it is difficult to achieve and sustain large weight losses.

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Calorie-Restricted Weight Loss Reverses High-Fat Diet-Induced Ghrelin Resistance, Which Contributes to Rebound Weight Gain in a Ghrelin-Dependent Manner

Endocrinology ◽

10.1210/en.2012-1421 ◽

2013 ◽

Vol 154 (2) ◽

pp. 709-717 ◽

Cited By ~ 44

Author(s):

Dana I. Briggs ◽

Sarah H. Lockie ◽

Qunli Wu ◽

Moyra B. Lemus ◽

Romana Stark ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Weight Gain ◽

High Fat Diet ◽

Chow Diet ◽

Dependent Manner ◽

High Fat ◽

Dietary Interventions ◽

Set Point ◽

Reduced Body

Twelve weeks of high-fat diet feeding causes ghrelin resistance in arcuate neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons. In the current study, we investigated whether diet-induced weight loss could restore NPY/AgRP neuronal responsiveness to ghrelin and whether ghrelin mediates rebound weight gain after calorie-restricted (CR) weight loss. Diet-induced obese (DIO) mice were allocated to one of two dietary interventions until they reached the weight of age-matched lean controls. DIO mice received chow diet ad libitum or chow diet with 40% CR. Chow-fed and high-fat–fed mice served as controls. Both dietary interventions normalized body weight, glucose tolerance, and plasma insulin. We show that diet-induced weight loss with CR increases total plasma ghrelin, restores ghrelin sensitivity, and increases hypothalamic NPY and AgRP mRNA expression. We propose that long-term DIO creates a higher body weight set-point and that weight loss induced by CR, as seen in the high-fat CR group, provokes the brain to protect the new higher set-point. This adaptation to weight loss likely contributes to rebound weight gain by increasing peripheral ghrelin concentrations and restoring the function of ghrelin-responsive neuronal populations in the hypothalamic arcuate nucleus. Indeed, we also show that DIO ghrelin-knockout mice exhibit reduced body weight regain after CR weight loss compared with ghrelin wild-type mice, suggesting ghrelin mediates rebound weight gain after CR weight loss.

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Managing Obesity in Lockdown: Survey of Health Behaviors and Telemedicine

Nutrients ◽

10.3390/nu13041359 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1359

Author(s):

Noga C Minsky ◽

Dafna Pachter ◽

Galia Zacay ◽

Naama Chishlevitz ◽

Miriam Ben-Hamo ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Weight Gain ◽

Health Behaviors ◽

Online Survey ◽

Eating Patterns ◽

Weight Changes ◽

Exercise Habits ◽

Prevent Weight Gain ◽

Vegetables And Fruits

Since the outbreak of COVID-19, billions of people have gone into lockdown, facing pandemic related challenges that engender weight gain, especially in the obese. We report the results of an online survey, conducted during Israel’s first quarantine, of 279 adults treated in hospital-based obesity clinics with counseling, medications, surgery, endoscopic procedures, or any combination of these for weight loss. In this study, we assessed the association between changes in dietary and lifestyle habits and body weight, and the benefits of receiving weight management care remotely through telemedicine during lockdown. Compared to patients not receiving obesity care via telemedicine, patients receiving this care were more likely to lose weight (OR, 2.79; p = 0.042) and also to increase participation in exercise (OR, 2.4; p = 0.022). While 40% of respondents reported consuming more sweet or salty processed snacks and 33% reported less vegetables and fruits, 65% reported more homemade foods. At the same time, 40% of respondents reported a reduction in exercise and 52% reported a decline in mood. Alterations in these eating patterns, as well as in exercise habits and mood, were significantly associated with weight changes. This study highlights that lockdown affects health behaviors associated with weight change, and advocates for the use of telemedicine to provide ongoing obesity care during future quarantines in order to promote weight loss and prevent weight gain.

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Insulin and central regulation of spontaneous fattening and weight loss

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1985.249.2.r203 ◽

1985 ◽

Vol 249 (2) ◽

pp. R203-R208

Author(s):

R. B. Melnyk ◽

J. M. Martin

Keyword(s):

Weight Loss ◽

Body Weight ◽

Weight Gain ◽

Energy Balance ◽

Binding Capacity ◽

Insulin Receptors ◽

Insulin Binding ◽

Strong Positive Correlation ◽

Central Regulation ◽

Isolated Pancreatic Islets

Insulin binding to receptors in a partially purified hypothalamic membrane preparation is altered by prolonged starvation. To define further the relationship between hypothalamic insulin binding and energy balance, we studied the Richardson's ground squirrel, a hibernator that exhibits spontaneous 6- to 8-mo body weight cycles when kept in constant conditions. Isolated pancreatic islets from squirrels killed during the weight gain phase had greater glucose-stimulated insulin secretion than those from weight loss phase animals, and adipocytes showed significantly greater glucose incorporation into total lipid in response to insulin. Differences in lipogenesis were not attributable to changes in insulin-binding capacity. Hypothalamic tissue from weight gain phase animals bound more insulin than that from weight loss phase animals. Maximal binding was correlated with pancreatic islet responsiveness and maximal insulin-stimulated lipogenesis. The strong positive correlation between peripheral metabolic events associated with spontaneous alterations in energy balance and the binding kinetics of hypothalamic insulin receptors suggests that insulin may play an important role in the central regulation of body weight.

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Impact of Experimentally Induced Cognitive Dietary Restraint on Eating Behavior Traits, Appetite Sensations, and Markers of Stress during Energy Restriction in Overweight/Obese Women

Journal of Obesity ◽

10.1155/2018/4259389 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

Isabelle Morin ◽

Catherine Bégin ◽

Julie Maltais-Giguère ◽

Alexandra Bédard ◽

André Tchernof ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Eating Behavior ◽

Perceived Stress ◽

Negative Impact ◽

Dietary Restraint ◽

Premenopausal Women ◽

Energy Restriction ◽

Obese Women ◽

Experimentally Induced

Weight loss has been associated with changes in eating behaviors and appetite sensations that favor a regain in body weight. Since traditional weight loss approaches emphasize the importance of increasing cognitive dietary restraint (CDR) to achieve negative energy imbalance, it is difficult to untangle the respective contributions of energy restriction and increases in CDR on factors that can eventually lead to body weight regain. The present study aimed at comparing the effects of energy restriction alone or in combination with experimentally induced CDR on eating behavior traits, appetite sensations, and markers of stress in overweight and obese women. We hypothesized that the combination of energy restriction and induced CDR would lead to more prevalent food cravings, increased appetite sensations, and higher cortisol concentrations than when energy restriction is not coupled with induced CDR. A total of 60 premenopausal women (mean BMI: 32.0 kg/m2; mean age: 39.4 y) were provided with a low energy density diet corresponding to 85% of their energy needs during a 4-week fully controlled period. At the same time, women were randomized to either a condition inducing an increase in CDR (CDR+ group) or a condition in which CDR was not induced (CRD− group). Eating behavior traits (Three-Factor Eating Questionnaire and Food Craving Questionnaire), appetite sensations (after standardized breakfast), and markers of stress (Perceived Stress Scale; postawakening salivary cortisol) were measured before (T = 0 week) and after (T = 4 weeks) the 4-week energy restriction, as well as 3 months later. There was an increase in CDR in the CDR+ group while no such change was observed in the CDR− group (p=0.0037). No between-group differences were observed for disinhibition, hunger, cravings, appetite sensations, perceived stress, and cortisol concentrations. These results suggest that a slight increase in CDR has no negative impact on factors regulating energy balance in the context of energy restriction.

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Front Cover: Nicotinamide Protects Against Diet‐Induced Body Weight Gain, Increases Energy Expenditure, and Induces White Adipose Tissue Beiging

Molecular Nutrition & Food Research ◽

10.1002/mnfr.202170027 ◽

2021 ◽

Vol 65 (11) ◽

pp. 2170027

Author(s):

Karen Alejandra Méndez‐Lara ◽

Elisabeth Rodríguez‐Millán ◽

David Sebastián ◽

Rosi Blanco‐Soto ◽

Mercedes Camacho ◽

...

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Energy Expenditure ◽

White Adipose Tissue ◽

Body Weight Gain ◽

Front Cover

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MO704THE PROGNOSTIC IMPACT OF WEIGHT GAIN AFTER PERITONEAL DIALYSIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab101.0026 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Win Hlaing Than ◽

Jack K C Ng ◽

Gordon C K Chan ◽

Winston Fung ◽

Cheuk Chun Szeto

Keyword(s):

Weight Loss ◽

Body Weight ◽

Peritoneal Dialysis ◽

Weight Gain ◽

Clinical Outcomes ◽

Patient Survival ◽

Survival Rates ◽

Overweight And Obesity ◽

Technique Survival ◽

Technique Failure

Abstract Background and Aims The prevalence of obesity has increased over the past decade in patients with End Stage Kidney Disease (ESKD). Obesity at the initiation of peritoneal dialysis (PD) was reported to adversely affect clinical outcomes. However, there are few studies on the prognostic relevance of weight gain after PD. Method We reviewed the change in body weight of 954 consecutive PD patients from the initiation of dialysis to 2 years after they remained on PD. Clinical outcomes including patient survival, technique survival, and peritonitis rate in the subsequent two years were reviewed. Results The mean age was 60.3 ± 12.2 years; 535 patients (56.1%) were men and 504 (52.8%) had diabetes. After the first 2 years on PD, the average change in body weight was 1.2± 5.1 kg; their body weight was 63.0 ± 13.3 kg; body mass index (BMI) 24.4 ± 4.4 kg/m2. The patient survival rates in the subsequent two years were 64.9%, 75.0%, and 78.9% (log rank test, p = 0.008) for patients with weight loss ≥3 kg during the first 2 years of PD weight change between -3 and +3 kg, and weight gain ≥3 kg, respectively. The corresponding technique survival rates in the subsequent two years were 93.1%, 90.1%, 91.3%, respectively (p = 0.110), and the peritonitis rates were 0.7±1.5, 0.6±1.7, and 0.6±1.1 episodes per patient-year, respectively (p = 0.3). When the actual BMI after the first 2 years of PD was categorized into underweight, normal weight, marginal overweight, overweight, and obesity groups, the patient survival rates in the subsequent two years were 77.3%, 75.2%, 73.3%, 74.3%, and 75.9%, respectively (p= 0.005), and technique survival 98.0%, 91.9%, 88.0%, 92.8%, and 81.0%, respectively (p= 0.001). After adjusting for confounding clinical factors by multivariate Cox regression models, weight gain ≥ 3kg during the first 2 years of PD was an independent protective factor for technique failure (adjusted hazard ratio [AHR] 0.049; 95% confidence interval [CI] 0.004-0.554, p = 0.015), but was an adverse predictor of patient survival (AHR 2.338, 95%CI 1.149-4.757, p = 0.019). In contrast, weight loss ≥ 3kg during the first 2 years of PD did not predict subsequent patient or technique survival. Conclusion Weight gain during the first 2 years of PD confers a significant risk of subsequent mortality but appears to be associated with a lower risk of technique failure. The mechanism of this discordant risk prediction deserves further study.

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Brown adipose tissue activation in a rat model of Parkinson’s disease

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00049.2017 ◽

2017 ◽

Vol 313 (6) ◽

pp. E731-E736 ◽

Cited By ~ 5

Author(s):

Wenjuan Wang ◽

Xiangzhi Meng ◽

Chun Yang ◽

Dongliang Fang ◽

Xuemeng Wang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Weight Loss ◽

Body Weight ◽

Adipose Tissue ◽

Energy Expenditure ◽

Brown Adipose Tissue ◽

Energy Intake ◽

Rat Model ◽

Sympathetic Denervation ◽

Brown Adipose

Loss of body weight and fat mass is one of the nonmotor symptoms of Parkinson’s disease (PD). Weight loss is due primarily to reduced energy intake and increased energy expenditure. Whereas inadequate energy intake in PD patients is caused mainly by appetite loss and impaired gastrointestinal absorption, the underlying mechanisms for increased energy expenditure remain largely unknown. Brown adipose tissue (BAT), a key thermogenic tissue in humans and other mammals, plays an important role in thermoregulation and energy metabolism; however, it has not been tested whether BAT is involved in the negative energy balance in PD. Here, using the 6-hydroxydopamine (6-OHDA) rat model of PD, we found that the activity of sympathetic nerve (SN), the expression of Ucp1 in BAT, and thermogenesis were increased in PD rats. BAT sympathetic denervation blocked sympathetic activity and decreased UCP1 expression in BAT and attenuated the loss of body weight in PD rats. Interestingly, sympathetic denervation of BAT was associated with decreased sympathetic tone and lipolysis in retroperitoneal and epididymal white adipose tissue. Our data suggeste that BAT-mediated thermogenesis may contribute to weight loss in PD.

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Attitudes about Antidepressants: Influence of Information about Weight-Related Side Effects

Perceptual and Motor Skills ◽

10.2466/pms.2000.90.2.453 ◽

2000 ◽

Vol 90 (2) ◽

pp. 453-456 ◽

Cited By ~ 5

Author(s):

Thomas F. Cash ◽

Melissa A. Brown

Keyword(s):

Weight Loss ◽

Body Image ◽

Body Weight ◽

Weight Gain ◽

Side Effects ◽

College Women ◽

Antidepressant Drugs ◽

Antidepressant Medications ◽

Body Image Ideals ◽

Clinical Populations

Antidepressant drugs are frequently prescribed for women and have various side effects, including potential effects on body weight. This experiment examined the effects of information about the weight-related side effects of antidepressants on women's attitudes toward the drugs. 60 college women were randomly assigned to read about one of two drugs, fluoxetine (Prozac) or Imipramine (Tofranil). Participants were either told or not told about veridical weight-related side effects, namely, weight loss for Prozac and weight gain for Tofranil. As hypothesized, weight-gain information lowered the personal acceptability of Tofranil, and weight-loss information enhanced the acceptability of Prozac. Although research with clinical populations is required, undergraduate women's decisions about the use of antidepressant medications may be influenced by societal body-image ideals.

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