Developmental Origins of Common Disease: Epigenetic Contributions to Obesity

Kappil, Maya; Wright, Robert O.; Sanders, Alison P.

doi:10.1146/annurev-genom-090314-050057

Cited by 23 publications

(18 citation statements)

References 43 publications

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“…While breastfeeding protects against later obesity in humans [96] , animal data suggest that milk composition can program offspring with higher risk of obesity and metabolic diseases [97] , [98] . For further examples on the developmental origin of metabolic diseases and particularly obesity, we suggest the following review [99] .…”

Section: Non-mendelian Phenotypic Variationmentioning

confidence: 99%

Epigenetic control of variation and stochasticity in metabolic disease

Panzeri

Pospisilik

2018

Molecular Metabolism

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BackgroundThe alarming rise of obesity and its associated comorbidities represents a medical burden and a major global health and economic issue. Understanding etiological mechanisms underpinning susceptibility and therapeutic response is of primary importance. Obesity, diabetes, and metabolic diseases are complex trait disorders with only partial genetic heritability, indicating important roles for environmental programing and epigenetic effects.Scope of the reviewWe will highlight some of the reasons for the scarce predictability of metabolic diseases. We will outline how genetic variants generate phenotypic variation in disease susceptibility across populations. We will then focus on recent conclusions about epigenetic mechanisms playing a fundamental role in increasing variability and subsequently disease triggering.Major conclusionsCurrently, we are unable to predict or mechanistically define how “missing heritability” drives disease. Unravelling this black box of regulatory processes will allow us to move towards a truly personalized and precision medicine.

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Section: Non-mendelian Phenotypic Variationmentioning

confidence: 99%

Epigenetic control of variation and stochasticity in metabolic disease

Panzeri

Pospisilik

2018

Molecular Metabolism

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“…Childhood and adolescent obesity are escalating global health challenges with a growing risk of the development of T2DM in these age groups or in their adulthood [2,3,[5][6][7]. The increased prevalence of childhood obesity was recognized mainly in developed and developing countries including the Saudi Arabia [4,23].…”

Section: Discussionmentioning

confidence: 99%

Association between circulating microRNAs 486, 146b and 15b and serum betatrophin levels in obese; type 2 diabetic and non-diabetic children

Mohany

Alrugaie

Al‐Wutayd

et al. 2020

Preprint

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Background: This study tested the association between serum levels of microRNA-486, -146b and -15b and betatrophin in normal and obese children with/without type 2 diabetes mellitus (T2DM).Methods: the study included 120 children; divided into three groups: G1 (50 healthy), G2 (35 obese) and G3 (35 obese with T2DM). The levels of microRNA-486, 146b and 15b and serum betatrophin were measured by their corresponding methods.Results: serum microRNA-486, -146b, -15b and betatrophin levels were significantly high in G3 followed by G2 then G1 (p=0.002, >0.001, >0.001, and >0.001, respectively). Especially in G3, these levels correlated positively with the BMI percentile (r=0.44, 0.58, 0.38, and 0.46, p=0.007, >0.001, 0.021, and 0.005, respectively), serum glucose (r=0.56, 0.49, 0.82, 0.60, and 0.42, p>0.001, 0.003, >0.001, and >0.001, respectively) and HbA1c% (r=0.56, 0.39, 0.66, and 0.42, p>0.001, 0.019, >0.001, and 0.032, respectively) while, showed negative correlations with correlated with serum insulin levels (r=-0.37, -0.42, -0.58, and -0.41, p=0.021, 0.012, >0.001 and 0.013, respectively) and with serum C-peptide levels (r=-0.76, -0.50, -0.35 and -0.42, p>0.001, 0.002, 0.036 and 0.011, respectively). Serum betatrophin levels correlated positively with microRNA-486, -146b and -15b levels in G2 (r=0.35, 0.80, and 0.67, p= 0.036, >0.001, and,>0.001, respectively), and in G3 (r=0.57, 0.36, and 0.38, p >0.001, 0.029 and, 0.023, respectively).Conclusions: Circulating microRNA-486, 146b and 15b increase significantly in obese children with T2DM and these levels correlate positively with serum betatrophin levels. Further studies are required to test the role of targeting of these microRNAs and betatrophin in the timely management of obesity and/or T2DM in children.

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“…The ‘developmental origins of health and disease’ theory states that environmental and dietary events in perinatal life can temporarily or permanently alter an organism’s physiology ( 4 ). The physiological alterations can program resistance or susceptibility to disease, and thus dietary events during perinatal life may also contribute to the increase in obesity and MetS in childhood and adulthood ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Insulinotropic Effect of S-Allyl Cysteine in Rat Pups

Lembede

Joubert

Nkomozepi

et al. 2018

pnf

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S-Allyl cysteine (SAC) is found in garlic and has been reported to exert antidiabetic and antiobesity properties in drug-induced adult experimental models of metabolic dysfunction, but its potential beneficial effects in high-fructose diet neonatal rat models have not been determined. This study investigated the potential prophylactic effects of SAC in high-fructose diet fed suckling rat pups modelling human neonates fed a high-fructose diet. Four-day-old male (n=32) and female (n=32) Wistar rat pups, were randomly assigned to and administered the following treatment regimens daily for 15 days: group I, distilled water; group II, 20% fructose solution (FS); group III, SAC; group IV, SAC+FS. The pups’ blood glucose, triglyceride, cholesterol, plasma leptin and insulin concentration, liver lipid content, and liver histology were determined at termination. In female rat pups, orally administered SAC prevented FS-induced hypoinsulinemia but significantly increased (P≤0.05) liver lipid content. Oral administration of SAC significantly increased (P≤0.05) plasma insulin concentration and homeostasis model assessment for insulin resistance in the male pups. The potential sexually dimorphic effects of SAC (insulinotropic effects in male pups and protection of female pups against fructose-induced hypoinsulinemia) suggest that SAC could be potentially exploited as an antidiabetic and insulinotropic agent. Caution should, however, be exercised in the use of SAC during suckling as it could result in excessive liver lipid accumulation and insulin resistance.

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Developmental Origins of Common Disease: Epigenetic Contributions to Obesity

Cited by 23 publications

References 43 publications

Epigenetic control of variation and stochasticity in metabolic disease

Epigenetic control of variation and stochasticity in metabolic disease

Association between circulating microRNAs 486, 146b and 15b and serum betatrophin levels in obese; type 2 diabetic and non-diabetic children

Insulinotropic Effect of S-Allyl Cysteine in Rat Pups

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