Rare genetic causes of obesity: Diagnosis and management in clinical care

Dubern, B.; Mosbah, H.; Pigeyre, Marie; Clément, Karine; Poitou, Christine

doi:10.1016/j.ando.2021.12.003

Cited by 25 publications

(8 citation statements)

References 42 publications

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“…Obesity has become a growing global problem and is regularly correlated with a wide spectrum of complications, including metabolic disorders, diabetes, cognitive dysfunction, cardiovascular diseases, hepatobiliary disease, and colon mucosal barrier impairment. [1][2][3] Obesity can cause grave financial, individual, and societal burdens in modern and future societies given its universal complications. 4 According to the World Health Organization (WHO), individuals with a body mass index (BMI) of > 30 kg/m2 are defined as obese.…”

Section: Introductionmentioning

confidence: 99%

Alpha-Linolenic Acid Ameliorates Cognitive Impairment and Liver Damage Caused by Obesity

Zhang,

Bao,

Zhang

et al. 2024

DMSO

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Background Obesity is a growing global problem that causes various complications such as diabetes, cognitive dysfunction, cardiovascular diseases, and hepatobiliary disease. Alpha-linolenic acid (ALA) has been reported to exhibit multiple pharmaceutical effects. This study aimed to explore the effects of ALA on obesity-induced adipose tissue accumulation, cognitive impairment, inflammation, and colonic mucosal barrier integrity. Methods Mice were fed with high-fat diet (HFD) and were treated with ALA (60 or 100 mg/kg). Body weight, adipose tissue, serum glucose and lipid levels, glucose resistance, and insulin resistance were measured. Cognitive ability was analyzed using the behavior tests. PTP1B and IRS/p-AKT/p-GSK3β/p-Tau signaling were examined to evaluate inflammation and synaptogenesis. Colon mucosal barrier integrity was examined by Alcian blue staining and expression of the tight junction proteins. The production of pro-inflammatory cytokines and liver damages were evaluated. 3T3-L1 cells were used for in vitro experiments. Cell viability, migration and invasion were detected. The levels of ROS, iron, and ferrous ions were measured to assess ferroptosis. Metabolomic analysis of adipose tissues was performed. Results ALA treatment prevented HFD-induced adipose tissue accumulation, improved glucose and lipid homeostasis and metabolism. Administration of ALA repressed the HFD-induced increase in insulin levels and insulin resistance index. Serum and colon levels of pro-inflammatory cytokines were decreased after ALA treatment. ALA elevated mitochondrial content in brown adipose tissues. ALA ameliorated obesity-induced cognitive impairment and hippocampal inflammation, enhanced colon mucosa integrity. ALA treatment ameliorated HFD-induced liver damage and lipid accumulation and inhibited differentiation of preadipocyte 3T3-L1 cells into mature adipocytes and induces ferroptosis. Metabolomic analysis suggested that ALA may target the glycerolipid metabolism pathway to ameliorate obesity. Knockdown of AGPAT2 abolished the protective effects of ALA. Conclusion ALA treatment suppressed adipose accumulation in adipocytes, improved cognitive ability and colon integrity, and alleviated liver damage by modulating the 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2).

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Section: Introductionmentioning

confidence: 99%

Alpha-Linolenic Acid Ameliorates Cognitive Impairment and Liver Damage Caused by Obesity

Zhang,

Bao,

Zhang

et al. 2024

DMSO

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“…The leptin/melanocortin pathway plays an undisputed role in the hypothalamic control of food intake. Its interruption due to a genetic defect is associated with early and severe obesity, with major hyperphagia in the first weeks of life, and with endocrine deficits and/or neurodevelopmental disorders [ 1 ]. These genetic obesities are a heavy burden for children and for their families, with deterioration in their quality of life.…”

Section: Introductionmentioning

confidence: 99%

Beneficial Effects of Setmelanotide in a 5-Year-Old Boy With POMC Deficiency and on His Caregivers

Dubern,

Lourdelle,

Clément

2023

JCEM Case Reports

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The melanocortin-4 receptor agonist setmelanotide is now recommended for the treatment of genetic obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency in patients aged 6 years and older. Here, we describe the clinical benefit of setmelanotide administration in a 5-year-old child with severe hyperphagia and obesity due to POMC deficiency. Daily administration of 0.5 mg setmelanotide for 12 months resulted in significant weight loss of −30 kg from baseline (−36% of weight loss) and improvements in hyperphagia and metabolic status. No major side effects were observed, except for hyperpigmentation and transient spontaneous erections. Interestingly, the clinical improvement of the child was associated with a remarkable improvement in the quality of life of the parents, along with a decrease in their emotional scores. This observation supports the early use of setmelanotide in young children with melanocortin pathway variants, in order to limit the adverse consequences of early and extreme weight gain, and to improve the quality of life of patients and of their relatives.

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“…The main cause of the onset of obesity is an imbalance between consumed and expended calories ( 1 ). Obesity has also been linked to genetic factors ( 6 , 7 ). However, in these last few decades evidence has mounted linking the increase of obesity worldwide to exposure to obesogens ( 8 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

Levels of Bisphenol A and its analogs in nails, saliva, and urine of children: a case control study

Gálvez-Ontiveros,

Moscoso-Ruiz,

Almazán Fernández de Bobadilla

et al. 2023

Front. Nutr.

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IntroductionA growing number of studies link the increase in overweight/obesity worldwide to exposure to certain environmental chemical pollutants that display obesogenic activity (obesogens). Since exposure to obesogens during the first stages of life has been shown to have a more intense and pronounced effect at lower doses, it is imperative to study their possible effects in childhood. The objective here was to study the association of Bisphenol A (BPA) and 11 BPA analogs in children, using three biological matrices (nails, saliva and urine), and overweight and obesity (n = 160).MethodsIn this case–control study, 59 overweight/obese children and 101 controls were included. The measuring of Bisphenols in the matrices was carried out by ultra-high performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC-MS/MS). Logistic regression was used to study the association between overweight/obesity and Bisphenol exposure.ResultsThe results suggested that BPF in nails is associated with overweight/ obesity in children (OR:4.87; p = 0.020). In saliva, however, the highest detected concentrations of BPAF presented an inverse association (OR: 0.06; p = 0.010) with overweight/obesity. No associations of statistical significance were detected between exposure to BPA or its other analogs and overweight/obesity in any of the biological matrices.

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Rare genetic causes of obesity: Diagnosis and management in clinical care

Cited by 25 publications

References 42 publications

Alpha-Linolenic Acid Ameliorates Cognitive Impairment and Liver Damage Caused by Obesity

Alpha-Linolenic Acid Ameliorates Cognitive Impairment and Liver Damage Caused by Obesity

Beneficial Effects of Setmelanotide in a 5-Year-Old Boy With POMC Deficiency and on His Caregivers

Levels of Bisphenol A and its analogs in nails, saliva, and urine of children: a case control study

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