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Cardiovascular Research Feb 2024Obesity is a chronic disease associated with serious complications and increased mortality. Weight loss (WL) through lifestyle changes results in modest WL long-term...
Obesity is a chronic disease associated with serious complications and increased mortality. Weight loss (WL) through lifestyle changes results in modest WL long-term possibly due to compensatory biological adaptations (increased appetite and reduced energy expenditure) promoting weight gain. Bariatric surgery was until recently the only intervention that consistently resulted in ≥ 15% WL and maintenance. Our better understanding of the endocrine regulation of appetite has led to the development of new medications over the last decade for the treatment of obesity with main target the reduction of appetite. The efficacy of semaglutide 2.4 mg/week-the latest glucagon-like peptide-1 (GLP-1) receptor analogue-on WL for people with obesity suggests that we are entering a new era in obesity pharmacotherapy where ≥15% WL is feasible. Moreover, the WL achieved with the dual agonist tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide) for people with type 2 diabetes and most recently also obesity, indicate that combining the GLP-1 with other gut hormones may lead to additional WL compared with GLP-1 receptor analogues alone and in the future, multi-agonist molecules may offer the potential to bridge further the efficacy gap between bariatric surgery and the currently available pharmacotherapies.
Topics: Humans; Diabetes Mellitus, Type 2; Obesity; Glucagon-Like Peptide 1; Appetite; Weight Loss; Glucagon-Like Peptide-1 Receptor; Hypoglycemic Agents
PubMed: 36448672
DOI: 10.1093/cvr/cvac176 -
Advances in Nutrition (Bethesda, Md.) Jul 2023Epidemiologic evidence supports a positive association between ultraprocessed food (UPF) consumption and body mass index. This has led to recommendations to avoid UPFs... (Review)
Review
Epidemiologic evidence supports a positive association between ultraprocessed food (UPF) consumption and body mass index. This has led to recommendations to avoid UPFs despite very limited evidence establishing causality. Many mechanisms have been proposed, and this review critically aimed to evaluate selected possibilities for specificity, clarity, and consistency related to food choice (i.e., low cost, shelf-life, food packaging, hyperpalatability, and stimulation of hunger/suppression of fullness); food composition (i.e., macronutrients, food texture, added sugar, fat and salt, energy density, low-calorie sweeteners, and additives); and digestive processes (i.e., oral processing/eating rate, gastric emptying time, gastrointestinal transit time, and microbiome). For some purported mechanisms (e.g., fiber content, texture, gastric emptying, and intestinal transit time), data directly contrasting the effects of UPF and non-UPF intake on the indices of appetite, food intake, and adiposity are available and do not support a unique contribution of UPFs. In other instances, data are not available (e.g., microbiome and food additives) or are insufficient (e.g., packaging, food cost, shelf-life, macronutrient intake, and appetite stimulation) to judge the benefits versus the risks of UPF avoidance. There are yet other evoked mechanisms in which the preponderance of evidence indicates ingredients in UPFs actually moderate body weight (e.g., low-calorie sweetener use for weight management; beverage consumption as it dilutes energy density; and higher fat content because it reduces glycemic responses). Because avoidance of UPFs holds potential adverse effects (e.g., reduced diet quality, increased risk of food poisoning, and food wastage), it is imprudent to make recommendations regarding their role in diets before causality and plausible mechanisms have been verified.
Topics: Humans; Obesity; Food; Diet; Body Weight; Energy Intake; Food Handling; Fast Foods
PubMed: 37080461
DOI: 10.1016/j.advnut.2023.04.006 -
Current Biology : CB Nov 2023López and Nogueiras introduce the peptide ghrelin and its physiological functions, including its roles in stimulating appetite and growth hormone release.
López and Nogueiras introduce the peptide ghrelin and its physiological functions, including its roles in stimulating appetite and growth hormone release.
Topics: Ghrelin; Growth Hormone; Appetite
PubMed: 37935121
DOI: 10.1016/j.cub.2023.09.009 -
Diabetes, Obesity & Metabolism Aug 2023To investigate the hypothesis that weight loss with the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide alone would lead to a greater reduction in the... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of the glucagon-like peptide-1 receptor agonist liraglutide, compared to caloric restriction, on appetite, dietary intake, body fat distribution and cardiometabolic biomarkers: A randomized trial in adults with obesity and prediabetes.
AIMS
To investigate the hypothesis that weight loss with the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide alone would lead to a greater reduction in the proportion of fat to lean tissue mass when compared to caloric restriction (CR) alone, as well as when compared to treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, that also enhances GLP-1 activity - to determine the independent effects of each treatment.
METHODS
A total of 88 adults with obesity and prediabetes were randomized to 14 weeks of intervention with CR (-390 kcal/d), liraglutide (1.8 mg/d), or the dipeptidyl peptidase-4 inhibitor sitagliptin (100 mg/d) as a weight-neutral comparator. Changes between groups in appetite and hunger ratings measured via visual analogue scales, dietary intakes, body weight, body composition via dual energy x-ray absorptiometry, and resting energy expenditure via indirect calorimetry were assessed using the Kruskal-Wallis test or Pearson's chi-squared test.
RESULTS
Weight loss ≥5% of baseline body weight occurred in 44% of participants in the CR group, 22% of the liraglutide group and 5% of the sitagliptin group (p = 0.02). The ratio of fat to lean mass decreased by 6.5% in the CR group, 2.2% in the liraglutide group, and 0% in the sitagliptin group (p = 0.02). Visceral fat reduced by 9.5% in the CR group, 4.8% in the liraglutide group, and 0% in the sitagliptin group (p = 0.04). A spontaneous reduction in dietary simple carbohydrates in the CR group was associated with improved homeostatic model assessment of insulin resistance score (HOMA-IR).
CONCLUSIONS
Although both liraglutide and CR are valuable strategies for cardiometabolic risk reduction, CR was associated with greater weight loss and more favourable improvements in body composition than treatment with liraglutide alone. Differences in the response to each of these interventions enables patients to be stratified to the most optimal intervention for their personal risk factors.
Topics: Humans; Adult; Liraglutide; Glucagon-Like Peptide-1 Receptor; Prediabetic State; Caloric Restriction; Appetite; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Sitagliptin Phosphate; Obesity; Dipeptidyl-Peptidase IV Inhibitors; Body Weight; Eating; Body Fat Distribution; Weight Loss; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Cardiovascular Diseases
PubMed: 37188932
DOI: 10.1111/dom.15113 -
Science Translational Medicine Nov 2023Remedies for the treatment of obesity date to Hippocrates, when patients with obesity were directed to "reduce food and avoid drinking to fullness" and begin "running... (Review)
Review
Remedies for the treatment of obesity date to Hippocrates, when patients with obesity were directed to "reduce food and avoid drinking to fullness" and begin "running during the night." Similar recommendations have been repeated ever since, despite the fact that they are largely ineffective. Recently, highly effective therapeutics were developed that may soon enable physicians to manage body weight in patients with obesity in a manner similar to the way that blood pressure is controlled in patients with hypertension. These medicines have grown out of a revolution in our understanding of the molecular and neural control of appetite and body weight, reviewed here.
Topics: Humans; Satiety Response; Obesity; Appetite; Body Weight
PubMed: 37992155
DOI: 10.1126/scitranslmed.adh4453 -
Cell Dec 2023The hedonic value of salt fundamentally changes depending on the internal state. High concentrations of salt induce innate aversion under sated states, whereas such...
The hedonic value of salt fundamentally changes depending on the internal state. High concentrations of salt induce innate aversion under sated states, whereas such aversive stimuli transform into appetitive ones under sodium depletion. Neural mechanisms underlying this state-dependent salt valence switch are poorly understood. Using transcriptomics state-to-cell-type mapping and neural manipulations, we show that positive and negative valences of salt are controlled by anatomically distinct neural circuits in the mammalian brain. The hindbrain interoceptive circuit regulates sodium-specific appetitive drive , whereas behavioral tolerance of aversive salts is encoded by a dedicated class of neurons in the forebrain lamina terminalis (LT) expressing prostaglandin E2 (PGE2) receptor, Ptger3. We show that these LT neurons regulate salt tolerance by selectively modulating aversive taste sensitivity, partly through a PGE2-Ptger3 axis. These results reveal the bimodal regulation of appetitive and tolerance signals toward salt, which together dictate the amount of sodium consumption under different internal states.
Topics: Animals; Neural Pathways; Sodium; Taste; Mice; Gene Expression Profiling
PubMed: 37989313
DOI: 10.1016/j.cell.2023.10.020