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Cell Metabolism Feb 2023GDF15 and its receptor GFRAL/RET form a non-homeostatic system that regulates food intake and body weight in preclinical species. Here, we describe a GDF15 analog,...
GDF15 and its receptor GFRAL/RET form a non-homeostatic system that regulates food intake and body weight in preclinical species. Here, we describe a GDF15 analog, LY3463251, a potent agonist at the GFRAL/RET receptor with prolonged pharmacokinetics. In rodents and obese non-human primates, LY3463251 decreased food intake and body weight with no signs of malaise or emesis. In a first-in-human study in healthy participants, single subcutaneous LY3463251 injections showed a safety and pharmacokinetic profile supporting further clinical development with dose-dependent nausea and emesis in a subset of individuals. A subsequent 12-week multiple ascending dose study in overweight and obese participants showed that LY3463251 induced significant decreases in food intake and appetite scores associated with modest body weight reduction independent of nausea and emesis (clinicaltrials.gov: NCT03764774). These observations demonstrate that agonism of the GFRAL/RET system can modulate energy balance in humans, though the decrease in body weight is surprisingly modest, suggesting challenges in leveraging the GDF15 system for clinical weight-loss applications.
Topics: Animals; Humans; Body Weight; Obesity; Weight Loss; Vomiting; Growth Differentiation Factor 15
PubMed: 36630958
DOI: 10.1016/j.cmet.2022.12.011 -
Nutrients Sep 2021The primary aim was to systematically review the current evidence investigating if dietary interventions rich in protein lead to improved body weight management in... (Meta-Analysis)
Meta-Analysis
Are Dietary Proteins the Key to Successful Body Weight Management? A Systematic Review and Meta-Analysis of Studies Assessing Body Weight Outcomes after Interventions with Increased Dietary Protein.
The primary aim was to systematically review the current evidence investigating if dietary interventions rich in protein lead to improved body weight management in adults with excessive body weight. The secondary aim was to investigate potential modifying effects of phenotyping. A systematic literature search in PubMed, Web of Science, and Cochrane Library identified 375 randomized controlled trials with 43 unique trials meeting the inclusion criteria. The Cochrane collaboration tool was used for a thorough risk of bias assessment. Based on 37 studies evaluating effects of dietary protein on body weight, the participants with increased protein intake (ranging from 18-59 energy percentage [E%]) were found to reduce body weight by 1.6 (1.2; 2.0) kg (mean [95% confidence interval]) compared to controls (isocaloric interventions with energy reduction introduced in certain studies). Individuals with prediabetes were found to benefit more from a diet high in protein compared to individuals with normoglycemia, as did individuals without the obesity risk allele (AA genotype) compared to individuals with the obesity risk alleles (AG and GG genotypes). Thus, diets rich in protein would seem to have a moderate beneficial effect on body weight management.
Topics: Adult; Body Mass Index; Body Weight; Diet, High-Protein; Dietary Proteins; Exercise; Female; Humans; Male; Middle Aged; Obesity; Overweight; Randomized Controlled Trials as Topic; Weight Gain; Weight Loss; Young Adult
PubMed: 34579069
DOI: 10.3390/nu13093193 -
The Journal of Clinical Endocrinology... Jul 2012An important goal during weight loss is to maximize fat loss while preserving metabolically active fat-free mass (FFM). Massive weight loss typically results in... (Clinical Trial)
Clinical Trial
CONTEXT
An important goal during weight loss is to maximize fat loss while preserving metabolically active fat-free mass (FFM). Massive weight loss typically results in substantial loss of FFM potentially slowing metabolic rate.
OBJECTIVE
Our objective was to determine whether a weight loss program consisting of diet restriction and vigorous exercise helped to preserve FFM and maintain resting metabolic rate (RMR).
PARTICIPANTS AND INTERVENTION
We measured body composition by dual-energy x-ray absorptiometry, RMR by indirect calorimetry, and total energy expenditure by doubly labeled water at baseline (n = 16), wk 6 (n = 11), and wk 30 (n = 16).
RESULTS
At baseline, participants were severely obese (× ± SD; body mass index 49.4 ± 9.4 kg/m(2)) with 49 ± 5% body fat. At wk 30, more than one third of initial body weight was lost (-38 ± 9%) and consisted of 17 ± 8% from FFM and 83 ± 8% from fat. RMR declined out of proportion to the decrease in body mass, demonstrating a substantial metabolic adaptation (-244 ± 231 and -504 ± 171 kcal/d at wk 6 and 30, respectively, P < 0.01). Energy expenditure attributed to physical activity increased by 10.2 ± 5.1 kcal/kg.d at wk 6 and 6.0 ± 4.1 kcal/kg.d at wk 30 (P < 0.001 vs. zero).
CONCLUSIONS
Despite relative preservation of FFM, exercise did not prevent dramatic slowing of resting metabolism out of proportion to weight loss. This metabolic adaptation may persist during weight maintenance and predispose to weight regain unless high levels of physical activity or caloric restriction are maintained.
Topics: Absorptiometry, Photon; Adipose Tissue; Adult; Basal Metabolism; Body Composition; Body Weight; Combined Modality Therapy; Diet, Reducing; Down-Regulation; Exercise Therapy; Female; Humans; Male; Metabolic Diseases; Middle Aged; Obesity, Morbid; Weight Gain; Weight Loss; Weight Reduction Programs; Young Adult
PubMed: 22535969
DOI: 10.1210/jc.2012-1444 -
The New England Journal of Medicine Mar 1995No current treatment for obesity reliably sustains weight loss, perhaps because compensatory metabolic processes resist the maintenance of the altered body weight. We... (Clinical Trial)
Clinical Trial Comparative Study
BACKGROUND
No current treatment for obesity reliably sustains weight loss, perhaps because compensatory metabolic processes resist the maintenance of the altered body weight. We examined the effects of experimental perturbations of body weight on energy expenditure to determine whether they lead to metabolic changes and whether obese subjects and those who have never been obese respond similarly.
METHODS
We repeatedly measured 24-hour total energy expenditure, resting and nonresting energy expenditure, and the thermic effect of feeding in 18 obese subjects and 23 subjects who had never been obese. The subjects were studied at their usual body weight and after losing 10 to 20 percent of their body weight by underfeeding or gaining 10 percent by overfeeding.
RESULTS
Maintenance of a body weight at a level 10 percent or more below the initial weight was associated with a mean (+/- SD) reduction in total energy expenditure of 6 +/- 3 kcal per kilogram of fat-free mass per day in the subjects who had never been obese (P < 0.001) and 8 +/- 5 kcal per kilogram per day in the obese subjects (P < 0.001). Resting energy expenditure and nonresting energy expenditure each decreased 3 to 4 kcal per kilogram of fat-free mass per day in both groups of subjects. Maintenance of body weight at a level 10 percent above the usual weight was associated with an increase in total energy expenditure of 9 +/- 7 kcal per kilogram of fat-free mass per day in the subjects who had never been obese (P < 0.001) and 8 +/- 4 kcal per kilogram per day in the obese subjects (P < 0.001). The thermic effect of feeding and nonresting energy expenditure increased by approximately 1 to 2 and 8 to 9 kcal per kilogram of fat-free mass per day, respectively, after weight gain. These changes in energy expenditure were not related to the degree of adiposity or the sex of the subjects.
CONCLUSIONS
Maintenance of a reduced or elevated body weight is associated with compensatory changes in energy expenditure, which oppose the maintenance of a body weight that is different from the usual weight. These compensatory changes may account for the poor long-term efficacy of treatments for obesity.
Topics: Adult; Body Composition; Body Weight; Energy Intake; Energy Metabolism; Female; Food, Formulated; Humans; Male; Middle Aged; Obesity; Weight Gain; Weight Loss
PubMed: 7632212
DOI: 10.1056/NEJM199503093321001 -
Experimental Gerontology Apr 2023The aim of this study was to determine the effectiveness of a six-week time-restricted eating (TRE) intervention in reducing body weight, fat loss, and visceral fat in... (Randomized Controlled Trial)
Randomized Controlled Trial
The aim of this study was to determine the effectiveness of a six-week time-restricted eating (TRE) intervention in reducing body weight, fat loss, and visceral fat in overweight, older adult men and women (age range = 65-74 years). Another objective was to determine the feasibility of widespread use of TRE in older women and men. The study randomly assigned 116 healthy, non-smoking participants to one of two conditions: TRE or educational control participants. Participants in the TRE group were instructed to not consume calorie containing beverages or food for 16 h per day, from 8:00 pm to 12:00 pm. Participants in the control group were instructed to follow a meal plan based on their previous habits. The changes in body weight and body composition were determined using a SECA mBCA 515 analyzer. The six-week TRE intervention resulted in a significant decrease in body weight in both men and women (-1.8 kg and-1.3 kg, respectively; p = 0.03). In men, a significant decrease in visceral fat mass (-0.54 l; p ≤ 0.001) and waist circumference (-2.9 cm; p ≤ 0.015) was observed. No significant changes in either visceral fat or waist circumference were observed in women. Additionally, no change in skeletal muscle mass was observed in either the control or TRE group. More than 99 % of female and 98 % of male participants were able to adhere to the prescribed time-restricted eating (16/8) plan, suggesting that this dietary approach could have beneficial effects on the body composition of overweight older men and may also reduce body weight in overweight, older women.
Topics: Aged; Female; Humans; Male; Body Composition; Body Weight; Intra-Abdominal Fat; Obesity; Overweight; Weight Loss
PubMed: 36739795
DOI: 10.1016/j.exger.2023.112116 -
Journal of the American Association of... Aug 2023Psyllium is a natural, predominantly soluble fiber that forms a viscous gel when hydrated and is not digested or fermented. In the small intestine, psyllium gel... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Psyllium is a natural, predominantly soluble fiber that forms a viscous gel when hydrated and is not digested or fermented. In the small intestine, psyllium gel increases chyme viscosity, slowing the degradation and absorption of nutrients. Psyllium has a significant effect in patients with metabolic syndrome and type-2 diabetes on glycemic control, while lowering serum cholesterol in hypercholesterolemic patients. Some randomized controlled studies have shown that psyllium also facilitates weight loss in overweight and obese participants.
OBJECTIVES
A comprehensive review and meta-analysis assessing psyllium's impact on body weight, body mass index (BMI), and waist circumference in overweight and obese participants.
DATA SOURCES
A comprehensive search was performed (Medline, Scopus, Cochrane Database) through March 21, 2022, using search terms to identify randomized, controlled, clinical studies designed to assess weight loss in overweight and obese participants over at least 2 months. Data were analyzed using the inverse variance method with random effects models.
CONCLUSIONS
Six studies meeting inclusion criteria were identified (total n = 354). The meta-analysis showed that psyllium, dosed just before meals (mean dose 10.8 g/day, mean duration 4.8 months), was effective for decreasing body weight (MD = -2.1 kg [95% confidence interval [CI]: -2.6 to -1.6]; p < .001), BMI (MD = -0.8 kg/m 2 [95% CI: -1.0 to -0.6]; p < .001) and waist circumference (MD = -2.2 cm [95% CI: -2.9 to -1.4]; p < .001) in overweight and obese populations.
IMPLICATIONS FOR PRACTICE
Gel-forming nonfermented psyllium fiber, dosed just before meals, is effective in facilitating weight loss in overweight and obese participants.
Topics: Humans; Body Weight; Obesity; Overweight; Psyllium; Weight Loss
PubMed: 37163454
DOI: 10.1097/JXX.0000000000000882 -
Medicina 2019Both total caloric intake and consumption of free sugars is higher than recommended. This situation contributes, among many other factors, to the increase of overweight... (Review)
Review
Both total caloric intake and consumption of free sugars is higher than recommended. This situation contributes, among many other factors, to the increase of overweight and obesity in the population. To maintain the sweet taste of foods and beverages while reducing the caloric content and the amount of free sugars in said products, many people choose to replace sugary products in their diet for options containing noncaloric sweeteners. This change in their dietary choice is accompanied by an increasing number of consultations with health professionals about the effects that non-caloric sweeteners could have on their body weight. Results reported in different scientific publications seem contradictory in relation to this topic: some of them, showing a positive association between the consumption of non-caloric sweeteners and energy intake and body weight, while others reporting that the consumption of these additives -in replacement of sugar- may lead to a reduction in caloric intake and body weight. The main objective of this article is to review the available evidence on the consumption of non-caloric sweeteners in relation to body weight, thus providing another tool for health professionals to make nutritional recommendations based on the best available evidence.
Topics: Body Mass Index; Body Weight; Dietary Sugars; Energy Intake; Humans; Non-Nutritive Sweeteners; Obesity; Weight Loss
PubMed: 31048277
DOI: No ID Found -
Journal of Obesity 2019
Topics: Biomedical Research; Body Weight; Health Promotion; Humans; Nutrition Therapy; Nutritional Physiological Phenomena; Obesity; Policy Making; Weight Reduction Programs
PubMed: 30984424
DOI: 10.1155/2019/6798096 -
JPMA. the Journal of the Pakistan... Apr 2023This communication proposes the term "hidden obesity" to describe normal weight obesity, or increased adiposity without a corresponding increase in body mass index. It...
This communication proposes the term "hidden obesity" to describe normal weight obesity, or increased adiposity without a corresponding increase in body mass index. It uses the concept of hidden hunger to craft semantics which will generate greater attention to this condition from all stake-holders, including policymakers and planners. The article describes simple tools which can be used to suspect and confirm the diagnosis of hidden obesity. This phenotype is very commonly seen in the south Asian population.
Topics: Humans; Adiposity; Body Mass Index; Obesity; Body Weight; South Asian People
PubMed: 37052022
DOI: 10.47391/JPMA.23-28 -
Molecular Metabolism Oct 2022Body weight is defended by strong homeostatic forces. Several of the key biological mechanisms that counteract weight loss have been unraveled over the last decades. In... (Review)
Review
BACKGROUND
Body weight is defended by strong homeostatic forces. Several of the key biological mechanisms that counteract weight loss have been unraveled over the last decades. In contrast, the mechanisms that protect body weight and fat mass from becoming too high remain largely unknown. Understanding this aspect of energy balance regulation holds great promise for curbing the obesity epidemic. Decoding the physiological and molecular pathways that defend against weight gain can be achieved by an intervention referred to as 'experimental overfeeding'.
SCOPE OF THE REVIEW
In this review, we define experimental overfeeding and summarize the studies that have been conducted on animals. This field of research shows that experimental overfeeding induces a potent and prolonged hypophagic response that seems to be conserved across species and mediated by unidentified endocrine factors. In addition, the literature shows that experimental overfeeding can be used to model the development of non-alcoholic steatohepatitis and that forced intragastric infusion of surplus calories lowers survival from infections. Finally, we highlight studies indicating that experimental overfeeding can be employed to study the transgenerational effects of a positive energy balance and how dietary composition and macronutrient content might impact energy homeostasis and obesity development in animals.
MAJOR CONCLUSIONS
Experimental overfeeding of animals is a powerful yet underappreciated method to investigate the defense mechanisms against weight gain. This intervention also represents an alternative approach for studying the pathophysiology of metabolic liver diseases and the links between energy balance and infection biology. Future research in this field could help uncover why humans respond differently to an obesogenic environment and reveal novel pathways with therapeutic potential against obesity and cardiometabolic disorders.
Topics: Animals; Body Weight; Energy Intake; Energy Metabolism; Humans; Obesity; Weight Gain
PubMed: 35970448
DOI: 10.1016/j.molmet.2022.101573