Genetic Contributors to Obesity

Sivasubramanian, Ramya; Malhotra, Sonali

doi:10.1016/j.gtc.2023.03.005

Cited by 7 publications

(2 citation statements)

References 51 publications

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“…(b) Transmissible predisposition: it is based on the existing, proven but insufficiently defined genetic [33][34][35] and/or epigenetic [36,37] conditioning of MS development. Most of the MS syndromic diseases are known to be gene-related, at least partially [38][39][40][41]. (c) Socio-epidemiologic factors: developed in parallel to the growing human control of the environment, which allows for the setting and maintenance of an MS-favoring complex [42,43], but also by food insecurity [44].…”

Section: The Complexity Of Msmentioning

confidence: 99%

The Metabolic Syndrome, a Human Disease

Alemany

2024

IJMS

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This review focuses on the question of metabolic syndrome (MS) being a complex, but essentially monophyletic, galaxy of associated diseases/disorders, or just a syndrome of related but rather independent pathologies. The human nature of MS (its exceptionality in Nature and its close interdependence with human action and evolution) is presented and discussed. The text also describes the close interdependence of its components, with special emphasis on the description of their interrelations (including their syndromic development and recruitment), as well as their consequences upon energy handling and partition. The main theories on MS’s origin and development are presented in relation to hepatic steatosis, type 2 diabetes, and obesity, but encompass most of the MS components described so far. The differential effects of sex and its biological consequences are considered under the light of human social needs and evolution, which are also directly related to MS epidemiology, severity, and relations with senescence. The triggering and maintenance factors of MS are discussed, with especial emphasis on inflammation, a complex process affecting different levels of organization and which is a critical element for MS development. Inflammation is also related to the operation of connective tissue (including the adipose organ) and the widely studied and acknowledged influence of diet. The role of diet composition, including the transcendence of the anaplerotic maintenance of the Krebs cycle from dietary amino acid supply (and its timing), is developed in the context of testosterone and β-estradiol control of the insulin-glycaemia hepatic core system of carbohydrate-triacylglycerol energy handling. The high probability of MS acting as a unique complex biological control system (essentially monophyletic) is presented, together with additional perspectives/considerations on the treatment of this ‘very’ human disease.

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Section: The Complexity Of Msmentioning

confidence: 99%

The Metabolic Syndrome, a Human Disease

Alemany

2024

IJMS

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“…Although most cases of childhood obesity can be attributed to exogenous causes, approximately 3–10% of those with severe early-onset obesity (EOO) are due to genetic disorders [ 2 , 3 ]. The exact prevalence of monogenic obesity remains uncertain because this aspect of childhood obesity remains relatively understudied, and missed diagnoses are common [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical and molecular characterisation of children with monogenic obesity: a case series

George,

Navi,

Nanda

et al. 2024

pedm

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Objective To study the clinical profile and molecular diagnosis of children with severe early-onset non-syndromic monogenic obesity. Methods The clinical and molecular data (performed using whole exome sequencing) of 7 children with early-onset (< 5 years) non-syndromic monogenic obesity were extracted from the Obesity Clinic files and analysed retrospectively. Results The median (IQR) age at presentation was 18 (10.5–27) months. Of the 7 patients, 5 were boys, 3 had a history of parental consanguinity, and 4 had a family history of severe early-onset obesity. All patients exhibited hyperphagia and showed signs of insulin resistance. Dyslipidaemia and fatty liver were observed in 4. The variants identified in 6 patients included 2 in leptin receptor, and one each in melanocortin 4 receptor, pro-opiomelanocortin, leptin, and neurotrophic tyrosine kinase receptor type 2 genes. Notably, 4 of these variants were novel. Conclusion This case series provides valuable insights into the spectrum of genetic mutations associated with non-syndromic monogenic obesity in North Indian children. The findings underscore the significance of next-generation sequencing in identifying the aetiology of severe early-onset obesity.

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