Muscle dysfunction caused by loss of Magel2 in a mouse model of Prader-Willi and Schaaf-Yang syndromes

Prader-Willi syndrome is characterized by severe hypotonia in infancy, with decreased lean mass and increased fat mass in childhood followed by severe hyperphagia and consequent obesity. Scoliosis and other orthopaedic manifestations of hypotonia are common in children with Prader-Willi syndrome and cause significant morbidity. The relationships among hypotonia, reduced muscle mass and scoliosis have been difficult to establish. Inactivating mutations in one Prader-Willi syndrome candidate gene, MAGEL2, cause a Prader-Willi-like syndrome called Schaaf-Yang syndrome, highlighting the importance of loss of MAGEL2 in Prader-Willi syndrome phenotypes. Gene-targeted mice lacking Magel2 have excess fat and decreased muscle, recapitulating altered body composition in Prader-Willi syndrome. We now demonstrate that Magel2 is expressed in the developing musculoskeletal system, and that loss of Magel2 causes muscle-related phenotypes in mice consistent with atrophy caused by altered autophagy. Magel2-null mice serve as a preclinical model for therapies targeting muscle structure and function in children lacking MAGEL2 diagnosed with Prader-Willi or Schaaf-Yang syndrome.
Source: Human Molecular Genetics - Category: Genetics & Stem Cells Authors: Tags: ARTICLES Source Type: research

Related Links:

Our world is amidst a crucial overweight and obesity pandemic that continues to grow, with 2 billion of the world ’s population overweight and approximately 700 million adults with obesity.1 Once thought to be a disease of the rich and affluent, weight-related and metabolic diseases are on the rise across all socioeconomic classes and residential settings. The enduring physiologic and hormonal changes that oc cur with weight gain make sustainable weight loss with just diet and exercise, commonly known as lifestyle modification, not feasible for most people.
Source: Gastrointestinal Endoscopy - Category: Gastroenterology Authors: Tags: Original article Source Type: research
In this study, we explored the effect of β -Lapachone ( β L), a compound obtained from the bark of the lapacho tree, against obesity. In vivo administration of β L into either high fat diet (HFD)-induced obese C57BL6 mice and genetically obese Lepr -∕- mice prevented body weight gain, which was associated with tissue weight loss of white adipose tissue (WAT). In addition, β L elevated thermogenic proteins including uncoupling protein 1 (UCP1) and mitochondrial count in BAT and human adipose tissue-derived mesenchymal stem cells (hAMSCs). β L also induced AMP-activated protein kinase (AMPK) phosph...
Source: The American Journal of Chinese Medicine - Category: Complementary Medicine Authors: Tags: Am J Chin Med Source Type: research
In conclusion, yacon syrup has a postprandial decreasing effect glucose and insulin concentrations in adult women. This effect was not evident for triglyceride concentration.Clinical trial registry: RBR-33wf46. Available in: abstract
Source: Food Research International - Category: Food Science Source Type: research
Authors: Gan X, Xu W, Yu K Abstract Background: With the rapid economy development of China, the overweight and obesity rates of school-age children and adolescents in China have been on the rise. The purpose of this study is to explore how powerful an influence economic growth has on the weight of children and adolescents and examine the relationship between China's macroeconomic development and weight of children and adolescents in the past 30 years using provincial panel data collected from more than 1 million children and adolescents. Methods: Panel data from seven longitudinal surveys (1985, 1991, 1995, 2000, ...
Source: Childhood Obesity - Category: Eating Disorders & Weight Management Tags: Child Obes Source Type: research
Authors: McMaster CM, Gow ML, Neal R, Alexander S, Baur LA, Cohen J Abstract High rates of attrition from pediatric weight management services are well documented in the literature; however, studies reporting on acceptability of "real-world" services have not previously been reviewed. This narrative synthesis aimed to summarize quantitative and qualitative research reporting on satisfaction of families who attended a secondary or tertiary pediatric weight management service. Electronic databases were searched for studies of family and/or patient satisfaction with hospital-based pediatric weight management...
Source: Childhood Obesity - Category: Eating Disorders & Weight Management Tags: Child Obes Source Type: research
Publication date: Available online 17 October 2019Source: Physiology &BehaviorAuthor(s): Janelle A Skinner, Manohar L Garg, Christopher V Dayas, Tracy L BurrowsABSTRACTThe neuropeptide oxytocin is best known for its role during parturition and the milk-let down reflex. Recent evidence identifies a role for oxytocin in eating behaviour. After oxytocin administration, caloric intake is reduced with stronger inhibitory effects in individuals with obesity. Whether the experience of visual food cues affects secretion or circulating levels of oxytocin is unknown. This pilot study had three aims: 1) to measure fasting appetit...
Source: Physiology and Behavior - Category: Physiology Source Type: research
In this study, we purified and identified anti-obesity peptides from hazelnut protein hydrolysates by chromatography and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Subsequently, we evaluated the inhibitory effect of the synthetic peptide on adipogenesis in 3T3-L1 adipocytes by Oil Red O staining, reverse transcription polymerase chain reaction (RT-PCR) and western blot. The results showed that a novel synthetic pentapeptide, Arg-Leu-Leu-Pro-His (RLLPH), derived from the C3 fraction, attenuated adipogenesis by downregulating the expression of several mRNAs related to adipogenesis, including peroxisome prolif...
Source: Journal of Bioscience and Bioengineering - Category: Biomedical Science Source Type: research
Conclusions: If the general pediatrician bec omes more familiar with PWS, the diagnosis and treatment will start earlier, which is essential to improve the quality of life and care for these individuals.
Source: Revista Paulista de Pediatria - Category: Pediatrics Source Type: research
Prader- Willi Syndrome (PWS) is a multisystem genetic disorder. In infancy, patients are typically hypotonic and may fail to thrive, but as they grow older, many become obese and develop obstructive sleep apnoea (OSA). We aimed to determine the prevalence of the respiratory complications seen in our cohort of patients referred from a regional PWS clinic in London.We performed a retrospective casenote review of the 49 children with PWS seen from 2010 to 2016, highlighting conditions that could influence their respiratory status.The median age was 5.2[0.4-15.8][range]yrs, 27/49(55%)male, BMI z score 0.7[2.1] mean[SD]. Only 7...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: 7.1 Paediatric Respiratory Physiology and Sleep Source Type: research
Prader Willi syndrome, resulting from the partial deletion or  lack of expression of a region of genes on the paternal chromosome 15, has a number of phenotypic features which predispose affected patients to ventilatory problems. These include generalised hypotonia, abnormal arousal and ventilatory responses to hypoxia and hypercapnia, scoliosis and fre quently, obesity. The spectrum of the resulting respiratory complications thus runs from sleep disordered breathing, to aspiration and respiratory functional impairment.
Source: Paediatric Respiratory Reviews - Category: Respiratory Medicine Authors: Tags: Review Source Type: research
More News: Back Curves | Children | Eating Disorders & Weight Management | Genetics | Obesity | Orthopaedics | Prader-Willi Syndrome | Scoliosis