Impact of Genetic Variations and Epigenetic Mechanisms on the Risk of Obesity

Chiurazzi, Martina; Cozzolino, Mauro; Orsini, Roberta Clara; Maro, Martina Di; Minno, Matteo Nicola Dario Di; Colantuoni, Antonio

doi:10.3390/ijms21239035

Cited by 22 publications

(13 citation statements)

References 80 publications

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“…However, studies demonstrated that severe obesity develops from rare genetic mutations that affect genes of both leptin and its receptor ( 29 ), and lead to congenital leptin deficiency or leptin resistance ( 30 ). Other loci which have been implicated in severe childhood monogenic obesity include genes of the proopiomelanocortin (POMC), the melanocortin receptor 4 (MC4R), the protein convertase 1/3 (PC 1/3), the single-minded homolog 1 (SIM1), and the brain-derived neurotrophic factor (BDNF) ( 31 ). Obesity caused by mutations in POMC gene shows autosomal recessive inheritance, whereas those in MC4R are autosomal dominant ( 32 ).…”

Section: Genetics Of Pediatric Obesitymentioning

confidence: 99%

Genetics, epigenetics and transgenerational transmission of obesity in children

et al. 2022

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Sedentary lifestyle and consumption of high-calorie foods have caused a relentless increase of overweight and obesity prevalence at all ages. Its presently epidemic proportion is disquieting due to the tight relationship of obesity with metabolic syndrome and several other comorbidities which do call for urgent workarounds. The usual ineffectiveness of present therapies and failure of prevention campaigns triggered overtime a number of research studies which have unveiled some relevant aspects of obesity genetic and epigenetic inheritable profiles. These findings are revealing extremely precious mainly to serve as a likely extra arrow to allow the clinician’s bow to achieve still hitherto unmet preventive goals. Evidence now exists that maternal obesity/overnutrition during pregnancy and lactation convincingly appears associated with several disorders in the offspring independently of the transmission of a purely genetic predisposition. Even the pre-conception direct exposure of either father or mother gametes to environmental factors can reprogram the epigenetic architecture of cells. Such phenomena lie behind the transfer of the obesity susceptibility to future generations through a mechanism of epigenetic inheritance. Moreover, a growing number of studies suggests that several environmental factors such as maternal malnutrition, hypoxia, and exposure to excess hormones and endocrine disruptors during pregnancy and the early postnatal period may play critical roles in programming childhood adipose tissue and obesity. A deeper understanding of how inherited genetics and epigenetics may generate an obesogenic environment at pediatric age might strengthen our knowledge about pathogenetic mechanisms and improve the clinical management of patients. Therefore, in this narrative review, we attempt to provide a general overview of the contribution of heritable genetic and epigenetic patterns to the obesity susceptibility in children, placing a particular emphasis on the mother-child dyad.

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Section: Genetics Of Pediatric Obesitymentioning

confidence: 99%

Genetics, epigenetics and transgenerational transmission of obesity in children

et al. 2022

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“…Obesity is an interplay between genes, epigenetics and the environment, including lifestyle [ 9 ]. Genes’ regulation of obesity is either monogenic or polygenic and is often poorly understood.…”

Section: Introductionmentioning

confidence: 99%

APOE Polymorphism and Endocrine Functions in Subjects with Morbid Obesity Undergoing Bariatric Surgery

Farup

Jansen

Hestad

et al. 2022

Genes

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Background: Obesity is an interplay between genes and the environment, including lifestyle. The genetics of obesity is insufficiently understood. Apolipoprotein E (APOE) genetic polymorphism has been associated with a wide range of disorders. Knowing that some APOE alleles are associated with obesity and endocrine disorders that are common in obesity, the present study aimed at exploring associations between APOE polymorphisms and endocrine functions in subjects with obesity undergoing bariatric surgery. Methods: Analyses of hormones in blood collected before and one year after bariatric surgery were examined. The APOE alleles were grouped as follows: E2 = ε2ε2 + ε2ε3; E3 = ε3ε3 + ε2ε4; E4 = ε3ε4 + ε4ε4. The APOE groups were analysed as nominal and ordered groups (E2-E3-E4) with a linear mixed model to predict the hormonal effects of the groups. Results: Forty-nine women (79%) and thirteen (21%) men with a mean age of 47.7 (SD 8.5) years were included in the study. The adiponectin level was significantly lower (p < 0.05) in the E2 group compared with the E4 group. Adiponectin and cortisol were positively and negatively associated, respectively, with the ordered APOE groups. Conclusions: The ordered APOE groups E2-E3-E4 were significantly associated with high and low levels of adiponectin and cortisol, respectively. The findings indicate APOE-mediated effects on body weight and metabolic functions in subjects with morbid obesity.

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“…Obesity is the result of a combination of many factors, including environmental factors and the expression of some genes, and is heritable[ 7 ]. The heritability of obesity is generally 40–70%[ 8 ]. Genome-wide association studies (GWASs) have identified a large number of BMI-associated loci.…”

Section: Introductionmentioning

confidence: 99%

RNA modification-related variants in genomic loci associated with body mass index

et al. 2022

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Background Genome-wide association studies (GWASs) have identified hundreds of loci for body mass index (BMI), but functional variants in these loci are less known. The purpose of this study was to identify RNA modification-related SNPs (RNAm-SNPs) for BMI in GWAS loci. BMI-associated RNAm-SNPs were identified in a GWAS of approximately 700,000 individuals. Gene expression and circulating protein levels affected by the RNAm-SNPs were identified by QTL analyses. Mendelian randomization (MR) methods were applied to test whether the gene expression and protein levels were associated with BMI. Results A total of 78 RNAm-SNPs associated with BMI (P < 5.0 × 10–8) were identified, including 65 m6A-, 10 m1A-, 3 m7G- and 1 A-to-I-related SNPs. Two functional loss, high confidence level m6A-SNPs, rs6713978 (P = 6.4 × 10–60) and rs13410999 (P = 8.2 × 10–59), in the intron of ADCY3 were the top significant SNPs. These two RNAm-SNPs were associated with ADCY3 gene expression in adipose tissues, whole blood cells, the tibial nerve, the tibial artery and lymphocytes, and the expression levels in these tissues were associated with BMI. Proteins enriched in specific KEGG pathways, such as natural killer cell-mediated cytotoxicity, the Rap1 signaling pathway and the Ras signaling pathway, were affected by the RNAm-SNPs, and circulating levels of some of these proteins (ADH1B, DOCK9, MICB, PRDM1, STOM, TMPRSS11D and TXNDC12) were associated with BMI in MR analyses. Conclusions Our study identified RNAm-SNPs in BMI-related genomic loci and suggested that RNA modification may affect BMI by affecting the expression levels of corresponding genes and proteins.

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Impact of Genetic Variations and Epigenetic Mechanisms on the Risk of Obesity

Cited by 22 publications

References 80 publications

Genetics, epigenetics and transgenerational transmission of obesity in children

Genetics, epigenetics and transgenerational transmission of obesity in children

APOE Polymorphism and Endocrine Functions in Subjects with Morbid Obesity Undergoing Bariatric Surgery

RNA modification-related variants in genomic loci associated with body mass index

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