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The Journal of Clinical Endocrinology... Jun 2023Prader-Willi syndrome (PWS) is a rare neurobehavioral-metabolic disease caused by the lack of paternally expressed genes in the chromosome 15q11-q13 region,... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Prader-Willi syndrome (PWS) is a rare neurobehavioral-metabolic disease caused by the lack of paternally expressed genes in the chromosome 15q11-q13 region, characterized by hypotonia, neurocognitive problems, behavioral difficulties, endocrinopathies, and hyperphagia resulting in severe obesity if not controlled.
OBJECTIVE
The primary end point was change from baseline in hyperphagia using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT). Other end points included Global Impression Scores, and changes in body composition, behaviors, and hormones.
METHODS
In DESTINY PWS, a 13-week, randomized, double-blind, placebo-controlled, phase 3 trial, 127 participants with PWS aged 4 years and older with hyperphagia were randomly assigned 2:1 to diazoxide choline extended-release tablet (DCCR) or placebo.
RESULTS
DCCR did not significantly improve hyperphagia (HQ-CT least-square mean (LSmean) [SE] -5.94 [0.879] vs -4.27 [1.145]; P = .198), but did so in participants with severe hyperphagia (LSmean [SE] -9.67 [1.429] vs -4.26 [1.896]; P = .012). Two of 3 secondary end points were improved (Clinical Global Impression of Improvement [CGI-I]; P = .029; fat mass; P = .023). In an analysis of results generated pre-COVID, the primary (HQ-CT; P = .037) and secondary end points were all improved (CGI-I; P = .015; Caregiver Global Impression of Change; P = .031; fat mass; P = .003). In general, DCCR was well tolerated with 83.3% in the DCCR group experiencing a treatment-emergent adverse event and 73.8% in the placebo group (not significant).
CONCLUSION
DCCR did not significantly improve hyperphagia in the primary analysis but did in participants with severe baseline hyperphagia and in the pre-COVID analysis. DCCR treatment was associated with significant improvements in body composition and clinician-reported outcomes.
Topics: Humans; Prader-Willi Syndrome; Diazoxide; COVID-19; Obesity; Hyperphagia
PubMed: 36639249
DOI: 10.1210/clinem/dgad014 -
Cell Metabolism Feb 2024Food is a powerful natural reinforcer that guides feeding decisions. The vagus nerve conveys internal sensory information from the gut to the brain about nutritional...
Food is a powerful natural reinforcer that guides feeding decisions. The vagus nerve conveys internal sensory information from the gut to the brain about nutritional value; however, the cellular and molecular basis of macronutrient-specific reward circuits is poorly understood. Here, we monitor in vivo calcium dynamics to provide direct evidence of independent vagal sensing pathways for the detection of dietary fats and sugars. Using activity-dependent genetic capture of vagal neurons activated in response to gut infusions of nutrients, we demonstrate the existence of separate gut-brain circuits for fat and sugar sensing that are necessary and sufficient for nutrient-specific reinforcement. Even when controlling for calories, combined activation of fat and sugar circuits increases nigrostriatal dopamine release and overeating compared with fat or sugar alone. This work provides new insights into the complex sensory circuitry that mediates motivated behavior and suggests that a subconscious internal drive to consume obesogenic diets (e.g., those high in both fat and sugar) may impede conscious dieting efforts.
Topics: Humans; Sugars; Carbohydrates; Brain; Diet; Hyperphagia
PubMed: 38242133
DOI: 10.1016/j.cmet.2023.12.014 -
Nutrients Nov 2023Eating disorders and excessive attachment to social media are a matter of great concern among youths. This study assessed the prevalence of eating disorders and their...
Eating disorders and excessive attachment to social media are a matter of great concern among youths. This study assessed the prevalence of eating disorders and their association with social media addiction among youths. A descriptive cross-sectional study was conducted on 350 participants aged 14-25 years. Two pre-validated tools were used, i.e., the Eating Attitude Test and the Social Networking Addiction Scale. SPSS was used to analyze the data. Out of the 350 students, 42% had probable eating disorders, and 41.7% had social media addictions. The findings revealed that the chances of having eating disorders were significantly higher among youths who lived in separate places, smoked, and had a family history of eating disorders ( ≤ 0.05). Furthermore, the dieting domain displayed notably higher scores for youths living separately ( ≤ 0.05) and smokers ( ≤ 0.01). Moreover, the scores for bulimia and food preoccupation were significantly higher among participants who were married ( = 0.038), were smokers ( = 0.027), and had a family history of eating disorders ( = 0.001). Higher scores in the oral control domain were reported by females ( ≤ 0.05) and severely obese youths ( ≤ 0.01). Moreover, social media addiction was significantly higher among students aged 18-21 ( ≤ 0.01). Spearman's correlation revealed that social media addiction has a weak positive relationship with eating disorders ( = 0.133, ≤ 0.01), particularly bulimia and food preoccupation ( = 0.173, ≤ 0.001). This reflects the need to address the harmful consequences of social media addiction that might raise the likelihood of developing eating disorders, particularly bulimia nervosa.
Topics: Female; Humans; Adolescent; Bulimia; Internet Addiction Disorder; Prevalence; Cross-Sectional Studies; Anorexia Nervosa; Feeding and Eating Disorders; Bulimia Nervosa
PubMed: 37960340
DOI: 10.3390/nu15214687 -
Philosophical Transactions of the Royal... Oct 2023Genetic disruption of key molecular components of the hypothalamic leptin-melanocortin pathway causes severe obesity in mice and humans. Physiological studies in people... (Review)
Review
Genetic disruption of key molecular components of the hypothalamic leptin-melanocortin pathway causes severe obesity in mice and humans. Physiological studies in people who carry these mutations have shown that the adipose tissue-derived hormone leptin primarily acts to defend against starvation. A lack of leptin causes an intense drive to eat and increases the rewarding properties of food, demonstrating that human appetite has a strong biological basis. Genetic studies in clinical- and population-based cohorts of people with obesity or thinness continue to provide new insights into the physiological mechanisms involved in weight regulation and identify molecular targets for weight loss therapy. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.
Topics: Humans; Animals; Mice; Leptin; Thinness; Obesity; Adipose Tissue; Mutation
PubMed: 37661743
DOI: 10.1098/rstb.2022.0205 -
Nature Communications Dec 2023Mazdutide is a once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist. We evaluated the efficacy and safety of 24-week treatment of mazdutide up... (Randomized Controlled Trial)
Randomized Controlled Trial
Mazdutide is a once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist. We evaluated the efficacy and safety of 24-week treatment of mazdutide up to 6 mg in Chinese overweight adults or adults with obesity, as an interim analysis of a randomised, two-part (low doses up to 6 mg and high dose of 9 mg), double-blind, placebo-controlled phase 2 trial (ClinicalTrials.gov, NCT04904913). Overweight adults (body-mass index [BMI] ≥24 kg/m) accompanied by hyperphagia and/or at least one obesity-related comorbidity or adults with obesity (BMI ≥ 28 kg/m) were randomly assigned (3:1:3:1:3:1) to once-weekly mazdutide 3 mg, 4.5 mg, 6 mg or matching placebo at 20 hospitals in China. The primary endpoint was the percentage change from baseline to week 24 in body weight. A total of 248 participants were randomised to mazdutide 3 mg (n = 62), 4.5 mg (n = 63), 6 mg (n = 61) or placebo (n = 62). The mean percentage changes from baseline to week 24 in body weight were -6.7% (SE 0.7) with mazdutide 3 mg, -10.4% (0.7) with 4.5 mg, -11.3% (0.7) with 6 mg and 1.0% (0.7) with placebo, with treatment difference versus placebo ranging from -7.7% to -12.3% (all p < 0.0001). All mazdutide doses were well tolerated and the most common adverse events included diarrhoea, nausea and upper respiratory tract infection. In summary, in Chinese overweight adults or adults with obesity, 24-week treatment with mazdutide up to 6 mg was safe and led to robust and clinically meaningful body weight reduction.
Topics: Adult; Humans; Overweight; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Obesity; Body Weight; Glucagon-Like Peptide 1; Double-Blind Method; Treatment Outcome
PubMed: 38092790
DOI: 10.1038/s41467-023-44067-4 -
BioRxiv : the Preprint Server For... Aug 2023Cilia are near ubiquitous small, cellular appendages critical for cell-to-cell communication. As such, they are involved in diverse developmental and homeostatic...
Cilia are near ubiquitous small, cellular appendages critical for cell-to-cell communication. As such, they are involved in diverse developmental and homeostatic processes, including energy homeostasis. ARL13B is a regulatory GTPase highly enriched in cilia. Mice expressing an engineered ARL13B variant, ARL13B which retains normal biochemical activity, display no detectable ciliary ARL13B. Surprisingly, these mice become obese. Here, we measured body weight, food intake, and blood glucose levels to reveal these mice display hyperphagia and metabolic defects. We showed that ARL13B normally localizes to cilia of neurons in specific brain regions and pancreatic cells but is excluded from these cilia in the model. In addition to its GTPase function, ARL13B acts as a guanine nucleotide exchange factor (GEF) for ARL3. To test whether ARL13B's GEF activity is required to regulate body weight, we analyzed the body weight of mice expressing ARL13B, a variant that lacks ARL13B GEF activity for ARL3. We found no difference in body weight. Taken together, our results show that ARL13B functions within cilia to control body weight and that this function does not depend on its role as a GEF for ARL3. Controlling the subcellular localization of ARL13B in the engineered mouse model, ARL13B, enables us to define the cilia-specific role of ARL13B in regulating energy homeostasis.
PubMed: 37577625
DOI: 10.1101/2023.08.02.551695 -
Deutsches Arzteblatt International Feb 2024Eating disorders are seen mainly as a problem affecting women, not just by the public at large, but also in specialized circles. Although it is true that more women than... (Review)
Review
BACKGROUND
Eating disorders are seen mainly as a problem affecting women, not just by the public at large, but also in specialized circles. Although it is true that more women than men suffer from all types of eating disorder, pertinent reviews have clearly shown that they do indeed occur in men, and that the available evidence on the matter is limited. The stigmatization of men with eating disorders makes it harder for these men, and for the relevant professionals, to recognize the symptoms and to seek or provide help.
METHODS
This review is based on publications retrieved by a selective search in PubMed on the epidemiological, diagnostic, clinical, and therapeutic aspects of eating disorders in men.
RESULTS
Current estimated lifetime prevalences in men are 0.2% for anorexia nervosa, 0.6% for bulimia nervosa, and 1% for bingeeating disorder; the corresponding figures for women are 1.4%, 1.9%, and 2.8%. Men and women may display different manifestations. Women are thought to be mainly seeking a slim figure and weight reduction; men, a muscular build. The established Germanlanguage screening and diagnostic tools, however, do not cover the types of symptoms that are more common in men. Little is known about whether treatment yields comparable results in men and women.
CONCLUSION
It is important to combat the stigmati - zation of men with eating disorders and to remove the obstacles to their appropriate diagnosis and treatment. The current methods of screening and diagnosis need to be adapted to take account of the special aspects of abnormal eating behavior in men. It remains unclear whether and how the disorderspecific treatment of these conditions in men should differ from their treatment in women.
Topics: Male; Female; Humans; Bulimia; Feeding and Eating Disorders; Anorexia Nervosa
PubMed: 38019152
DOI: 10.3238/arztebl.m2023.0246