Genetics of Severe Obesity

Fairbrother, Una; Kidd, Elliot; Malagamuwa, Tanya; Walley, Andrew J.

doi:10.1007/s11892-018-1053-x

Cited by 69 publications

(51 citation statements)

References 109 publications

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“…Obesity linked to heterozygous variants of the MC4R gene represents approximately 2-3% of severe obesity in children and adults, with more than 166 different functional variants described in various populations (Europeans, Americans, Asians) (36). Children with heterozygous variants have more body fat than non-mutated BMI-matched subjects (37). It was initially reported that they are taller in the first 5 years of life (27) and more hyperphagic, but these characteristics may decrease with age.…”

Section: Clinical Subtypes Of Genetic Obesitymentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Update on treatments for patients with genetic obesity

Poitou

Mosbah

Clément

2020

European Journal of Endocrinology

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Obesity, defined by an excess of body fat impacting on health, is a complex disease resulting from the interaction between many genetic/epigenetic factors and environmental triggers. For clinical situations with severe obesity, it has been possible to classify these obesity forms according to the molecular alterations. These include: i) syndromic obesity, which associates severe early-onset obesity with neurodevelopmental disorders and/or polymalformative syndrome, and, ii) non-syndromic monogenic obesity, due to gene variants most often located in the leptin-melanocortin pathway. In addition to severe obesity, patients affected by these diseases display complex somatic conditions, eventually including obesity comorbidities, neuropsychological and psychiatric disorders. These conditions render the clinical management of these patients particularly challenging. Patients’ early diagnosis is critical to allow specialized and multidisciplinary care, with a necessary interaction between the health and social sectors. Up to now, the management of genetic obesity was only based, above all, on controlling the patient's environment, which involves limiting access to food, ensuring a reassuring daily eating environment that limits impulsiveness, and the practice of adapted, supported, and supervised physical activity. Bariatric surgery has also been undertaken in genetic obesity cases with uncertain outcomes. The context is rapidly changing, as new innovative therapies are currently being tested both for syndromic and monogenic forms of obesity. This review focuses on care management and new therapeutic opportunities in genetic obesity, including the use of the melanocortin 4 agonist, setmelanotide. The results from ongoing trials will hopefully pave the way to a future precision medicine approach for genetic obesity.

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Section: Clinical Subtypes Of Genetic Obesitymentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Update on treatments for patients with genetic obesity

Poitou

Mosbah

Clément

2020

European Journal of Endocrinology

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“…Severe obesity is known to be BMI with >35 kg/m 2 ; consists of obese I-IV ( Table 1 ). BMI is the only the tool used to evaluate frequencies of obesity in the adult-world population connected with health ( Fairbrother et al, 2018 ). Obesity associated diseases and disorders are amongst the leading cause of morbidity and mortality throughout the world.…”

Section: Introductionmentioning

confidence: 99%

Impact of weight loss predictors in severe-morbid obesity patients in the Saudi population

Al-Nbaheen

2020

Saudi Journal of Biological Sciences

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Universally, obesity has been affected more than 650 million and converts as global health problem. Obesity is equally affecting starting from children to elder population. Obese subjects are converting into severe obese and then into morbid obesity. Body mass index is proning from 30 to 50 kg/m 2 in the adult population. Obesity is connected with the future complications of hypertension, type 2 diabetes mellitus, cardiovascular, stroke, osteoarthritis, obstructive sleep apnea and liver diseases. Loosing of body fat is the only option to avoid obesity and this could be achieved with routine physical activity and diet modifications. Obesity subjects may fail to achieve the daily routine activities or insufficient activity may be involved and finally fail to lose the body fat after the medical course. Then these severe or morbidity obese can be lose with the existing surgery. Currently, Bariatric Surgery (BS) has become the active treatment for long-term weight loss. Various types (Roux-en-Y gastric bypass, sleeve gastrectomy and duodenal switch and the jejunoileal bypass) of BS are performed on the gastrointestinal tract. Throughout the world population, BS has found to be safe in losing the weight and avoiding the future and long-term complications. The prevalence of overweight and obesity in Saudi Arabia is an issue in terms of incidence and health consequences. Maximum obesity studies involved in Saudi Arabia has proven to be develop the long-term complications in the future involving from child to morbid obesity. Limited bariatric studies carried out in the Saudi subjects confirmed as effective tool in lowering the body fat and avoiding the life-threatened complications of human diseases. So, this review recommends BS as effective and safe surgical treatment to lose body fat in the Saudi population. However, post-operative monitoring is mandatory to follow-up.

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“…Starting from the discovery that several rare forms of obesity, called monogenic obesity, result from a mutation in single genes primarily located in the leptin–melanocortin pathway [15,16], recent evidence has identified additional selected genes associated with obesity, providing that the genetic background can play a pivotal role in causing or triggering susceptibility to the pathology when associated with environmental factors such as overeating and PE reduction [17,18]. Of note, brain-derived neurotrophic factor ( BDNF ) is included among these genes.…”

Section: Introductionmentioning

confidence: 99%

Physical Exercise Affects Adipose Tissue Profile and Prevents Arterial Thrombosis in BDNF Val66Met Mice

Sandrini

Ieraci

Amadio

et al. 2019

Cells

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Adipose tissue accumulation is an independent and modifiable risk factor for cardiovascular disease (CVD). The recent CVD European Guidelines strongly recommend regular physical exercise (PE) as a management strategy for prevention and treatment of CVD associated with metabolic disorders and obesity. Although mutations as well as common genetic variants, including the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, are associated with increased body weight, eating and neuropsychiatric disorders, and myocardial infarction, the effect of this polymorphism on adipose tissue accumulation and regulation as well as its relation to obesity/thrombosis remains to be elucidated. Here, we showed that white adipose tissue (WAT) of humanized knock-in BDNFVal66Met (BDNFMet/Met) mice is characterized by an altered morphology and an enhanced inflammatory profile compared to wild-type BDNFVal/Val. Four weeks of voluntary PE restored the adipocyte size distribution, counteracted the inflammatory profile of adipose tissue, and prevented the prothrombotic phenotype displayed, per se, by BDNFMet/Met mice. C3H10T1/2 cells treated with the Pro-BDNFMet peptide well recapitulated the gene alterations observed in BDNFMet/Met WAT mice. In conclusion, these data indicate the strong impact of lifestyle, in particular of the beneficial effect of PE, on the management of arterial thrombosis and inflammation associated with obesity in relation to the specific BDNF Val66Met mutation.

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Genetics of Severe Obesity

Cited by 69 publications

References 109 publications

MECHANISMS IN ENDOCRINOLOGY: Update on treatments for patients with genetic obesity

MECHANISMS IN ENDOCRINOLOGY: Update on treatments for patients with genetic obesity

Impact of weight loss predictors in severe-morbid obesity patients in the Saudi population

Physical Exercise Affects Adipose Tissue Profile and Prevents Arterial Thrombosis in BDNF Val66Met Mice

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