Syndrome de Bardet-Biedl : cils et obésité

Chennen, Kirsley; Scerbo, M. Julia; Dollfus, Hélène; Poch, Olivier; Marion, Vincent

doi:10.1051/medsci/20143011018

Cited by 18 publications

(4 citation statements)

References 70 publications

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“…The precise mechanisms involved in obesity development in BBS are still poorly understood. However, several hypotheses have been put forward (9,10). One proposes a central origin of obesity due to hypothalamic dysfunction associated with hyperphagia.…”

Section: Clinical Subtypes Of Genetic Obesitymentioning

confidence: 99%

“…For example, the loss of BBS proteins leads to synaptic aberrations in principal neurons, especially in structures such as the hippocampus and amygdala (11). Other hypotheses of a peripheral origin involving adipose tissue and adipocyte proliferation or other endocrine tissues (pancreas, stomach, intestine) have also been proposed (10).…”

Section: Clinical Subtypes Of Genetic Obesitymentioning

confidence: 99%

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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%

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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“…BBS proteins are, in particular, required for LEPR localization in the hypothalamus [ 23 ]. Other hypotheses of a peripheral origin from adipose tissue and adipocyte proliferation or other endocrine tissues (pancreas, stomach, intestine) were also proposed [ 25 ].…”

Section: Clinical Phenotypesmentioning

confidence: 99%

Rare Genetic Forms of Obesity: Clinical Approach and Current Treatments in 2016

Huvenne

Dubern²,

Clément³

et al. 2016

Obes Facts

190

191

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Obesity results from a synergistic relationship between genes and the environment. The phenotypic expression of genetic factors involved in obesity is variable, allowing to distinguish several clinical pictures of obesity. Monogenic obesity is described as rare and severe early-onset obesity with abnormal feeding behavior and endocrine disorders. This is mainly due to autosomal recessive mutations in genes of the leptin-melanocortin pathway which plays a key role in the hypothalamic control of food intake. Melanocortin 4 receptor(MC4R)-linked obesity is characterized by the variable severity of obesity and no notable additional phenotypes. Mutations in the MC4R gene are involved in 2-3% of obese children and adults; the majority of these are heterozygous. Syndromic obesity is associated with mental retardation, dysmorphic features, and organ-specific developmental abnormalities. Additional genes participating in the development of hypothalamus and central nervous system have been regularly identified. But to date, not all involved genes have been identified so far. New diagnostic tools, such as whole-exome sequencing, will probably help to identify other genes. Managing these patients is challenging. Indeed, specific treatments are available only for specific types of monogenic obesity, such as leptin deficiency. Data on bariatric surgery are limited and controversial. New molecules acting on the leptin-melanocortin pathway are currently being developed.

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“…A hypothalamic/neuro-endocrine dysfunction is thought to be critical in the development of obesity in the ciliopathies as feeding/satiety signaling is altered, likely due to the mislocalization of signaling receptors on neuronal cilia. Recent data is also highlighting an important role of the BBS proteins and cilia in maintaining peripheral tissue homeostasis, particularly in adipose tissue 10 , 27 – 29 . Several BBS proteins have been shown to change their abundance during adipogenesis while cilia are lost in mature adipocytes 30 , 31 .…”

Section: Introductionmentioning

confidence: 99%

BBS4 regulates the expression and secretion of FSTL1, a protein that participates in ciliogenesis and the differentiation of 3T3-L1

Prieto-Echagüe

Lodh

Colman

et al. 2017

Sci Rep

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Bardet-Biedl syndrome is a model ciliopathy. Although the characterization of BBS proteins has evidenced their involvement in cilia, extraciliary functions for some of these proteins are also being recognized. Importantly, understanding both cilia and cilia-independent functions of the BBS proteins is key to fully dissect the cellular basis of the syndrome. Here we characterize a functional interaction between BBS4 and the secreted protein FSTL1, a protein linked to adipogenesis and inflammation among other functions. We show that BBS4 and cilia regulate FSTL1 mRNA levels, but BBS4 also modulates FSTL1 secretion. Moreover, we show that FSTL1 is a novel regulator of ciliogenesis thus underscoring a regulatory loop between FSTL1 and cilia. Finally, our data indicate that BBS4, cilia and FSTL1 are coordinated during the differentiation of 3T3-L1 cells and that FSTL1 plays a role in this process, at least in part, by modulating ciliogenesis. Therefore, our findings are relevant to fully understand the development of BBS-associated phenotypes such as obesity.

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Syndrome de Bardet-Biedl : cils et obésité

Cited by 18 publications

References 70 publications

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

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

Rare Genetic Forms of Obesity: Clinical Approach and Current Treatments in 2016

BBS4 regulates the expression and secretion of FSTL1, a protein that participates in ciliogenesis and the differentiation of 3T3-L1

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