Peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala polymorphism and risk for pediatric obesity

Dedoussis, George; Vidra, Nikoleta V.; Butler, Johannah L.; Papoutsakis, Constantina; Yannakoulia, Mary; Hirschhorn, Joel N.; Lyon, Helen N.

doi:10.1515/cclm.2009.242

Cited by 19 publications

(18 citation statements)

References 22 publications

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“…Those metabolic parameters were not differently regulated in female obese participants, independent of the genotype. Similar results indicating sex-specific differences of obese patients and children with the Pro12Ala variant of PPARgamma2 were recently published by others (Dedoussis et al 2007(Dedoussis et al , 2009Morini et al 2008).…”

Section: Sex-specific Differences and Polymorphism Of Ppargammasupporting

confidence: 89%

Sex-Specific Differences in Type 2 Diabetes Mellitus and Dyslipidemia Therapy: PPAR Agonists

Benz

Kintscher

Foryst‐Ludwig

2012

Sex and Gender Differences in Pharmacology

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The influence of sex on the development of obesity, Type 2 Diabetes Mellitus (T2DM), and dyslipidemia is well documented, although the molecular mechanism underlying those differences reminds elusive. Ligands of peroxisome proliferator-activated receptors (PPARs) are used as oral antidiabetics (PPARgamma agonists: thiazolidinediones, TZDs), or for the treatment of dyslipidemia and cardiovascular diseases, due to their lipid-lowering properties (PPARalpha agonists: fibrates), as PPARs control transcription of a set of genes involved in the regulation of lipid and carbohydrate metabolism. Given a high prevalence of those metabolic disorders, and thus a broad use of PPAR agonists, the present review will discuss distinct aspects of sex-specific differences in antiobesity treatment using those groups of PPAR ligands.

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Section: Sex-specific Differences and Polymorphism Of Ppargammasupporting

confidence: 89%

Sex-Specific Differences in Type 2 Diabetes Mellitus and Dyslipidemia Therapy: PPAR Agonists

Benz

Kintscher

Foryst‐Ludwig

2012

Sex and Gender Differences in Pharmacology

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“…Research into variation at the PPARG locus and BMI has largely involved adults, but in a follow up study on weight and body composition, Pro12Ala was shown to regulate weight and body composition from birth through to adulthood (Pihlajamaki et al, 2004). Importantly, the alanine substitution has been associated with reduced BMI and increased insulin sensitivity in children (Buzzetti et al, 2005;Cecil et al, 2005;Dedoussis et al, 2009), indicating that this variant confers some sort of protection from obesity and type 2 diabetes at an early age. These data support much of the evidence in adults (Deeb et al, 1998;Doney et al, 2004), though reports are inconsistent (Hamann et al, 1999;Lagou et al, 2008;Scaglioni et al, 2006), possibly because of the action of multiple variants within the PPARG gene itself (Doney et al, 2004), and or other gene-gene and gene-environment interactions.…”

Section: Peroxisome Proliferator-activated Receptor Gene -A Candidatementioning

confidence: 99%

“…These data support much of the evidence in adults (Deeb et al, 1998;Doney et al, 2004), though reports are inconsistent (Hamann et al, 1999;Lagou et al, 2008;Scaglioni et al, 2006), possibly because of the action of multiple variants within the PPARG gene itself (Doney et al, 2004), and or other gene-gene and gene-environment interactions. In young children and peri-adolescents, this protection from an increased BMI is also associated with variation in measures of adiposity (Cecil et al, 2005;Dedoussis et al, 2009), suggesting that PPARG may infl uence fat deposition in childhood and well as adulthood. Emerging evidence in children suggests that PPARG Pro12Ala regulation of child adiposity (including measures of cholesterol/HDL and apoB/apoA1 ratios, skinfolds), may even be gender dependent (Dedoussis et al, 2009;Dedoussis et al, 2007;Lagou et al, 2008).…”

Section: Peroxisome Proliferator-activated Receptor Gene -A Candidatementioning

confidence: 99%

“…In young children and peri-adolescents, this protection from an increased BMI is also associated with variation in measures of adiposity (Cecil et al, 2005;Dedoussis et al, 2009), suggesting that PPARG may infl uence fat deposition in childhood and well as adulthood. Emerging evidence in children suggests that PPARG Pro12Ala regulation of child adiposity (including measures of cholesterol/HDL and apoB/apoA1 ratios, skinfolds), may even be gender dependent (Dedoussis et al, 2009;Dedoussis et al, 2007;Lagou et al, 2008).…”

Section: Peroxisome Proliferator-activated Receptor Gene -A Candidatementioning

confidence: 99%

“…PPARG also appears to affect food intake through heightened satiety (Rosado et al, 2007) and reduced fat intake, where the 12Ala variant was associated with reduced saturated fatty acid intake in adolescent girls (Dedoussis et al, 2009). In addition, PPARG genotype may infl uence child eating behaviour through variation in short-term energy compensation, a direct measure of satiety expression.…”

Section: Peroxisome Proliferator-activated Receptor Gene and Eating Bmentioning

confidence: 99%

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Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

Cecil

Dalton

Finlayson

et al. 2012

International Review of Psychiatry

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The prevalence of childhood obesity is increasing in many countries and confers risks for early type 2 diabetes, cardiovascular disease and metabolic syndrome. In the presence of potent ' obesogenic ' environments not all children become obese, indicating the presence of susceptibility and resistance. Taking an energy balance approach, susceptibility could be mediated through a failure of appetite regulation leading to increased energy intake or via diminished energy expenditure. Evidence shows that heritability estimates for BMI and body fat are paralleled by similar coeffi cients for energy intake and preferences for dietary fat. Twin studies implicate weak satiety and enhanced food responsiveness as factors determining an increase in BMI. Single gene mutations, for example in the leptin receptor gene, that lead to extreme obesity appear to operate through appetite regulating mechanisms and the phenotypic response involves overconsumption and a failure to inhibit eating. Investigations of robustly characterized common gene variants of fat mass and obesity associated ( FTO ), peroxisome proliferator-activated receptor ( PPARG ) and melanocortin 4 receptor ( MC4R ) which contribute to variance in BMI also infl uence the variance in appetite factors such as measured energy intake, satiety responsiveness and the intake of palatable energy-dense food. A review of the evidence suggests that susceptibility to childhood obesity involving specifi c allelic variants of certain genes is mediated primarily through food consumption (appetite regulation) rather than through a decrease in activity-related energy expenditure. This conclusion has implications for early detection of susceptibility, and for prevention and management of childhood obesity.

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The influence of clinical and genetic factors on the development of obesity in children with type 1 diabetes

Łuczyński

Głowińska-Olszewska

Bossowski

2016

Diabetes Metabolism Res

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The exact cause of the obesity epidemic remains unknown; however, both environmental and genetic factors are involved. People at risk of developing obesity include children with type 1 diabetes mellitus (T1DM), which in turn increases their cardiovascular disease risk. Here, we discuss the clinical and genetic factors influencing weight in patients with T1DM. In children with T1DM, the presence of obesity depends mainly on sex, metabolic control, and disease duration. However, genetic factors, including the fat mass and obesity-associated (FTO) gene, are also associated with body weight. Indeed, children with the FTO gene rs9939609 obesity-risk allele (homozygous = AA or heterozygous = AT) are predisposed to a higher body mass index and have a greater risk of being overweight or obese. However, in this review, we show that FTO gene polymorphisms only have a small effect on body weight in children, much weaker than the effect of clinical factors. The association between FTO gene polymorphisms and body weight is only statistically significant in children without severe obesity. Moreover, other genetic factors had no effect on weight in patients with T1DM, and further research involving larger populations is required to confirm the genetic basis of diabetes and obesity. Therefore, identifying the clinical features of children with T1DM, such as their initial body mass index, sex, metabolic control, and disease duration, will still have the strongest effect on reducing risk factors for cardiovascular diseases. Physicians should pay close attention to modifiable elements of these relationships, for example, metabolic control and energy and insulin intake, when caring for patients with T1DM. Copyright © 2016 John Wiley & Sons, Ltd.

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Peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala polymorphism and risk for pediatric obesity

Cited by 19 publications

References 22 publications

Sex-Specific Differences in Type 2 Diabetes Mellitus and Dyslipidemia Therapy: PPAR Agonists

Sex-Specific Differences in Type 2 Diabetes Mellitus and Dyslipidemia Therapy: PPAR Agonists

Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

The influence of clinical and genetic factors on the development of obesity in children with type 1 diabetes

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