Physical Activity Attenuates the Genetic Predisposition to Obesity in 20,000 Men and Women from EPIC-Norfolk Prospective Population Study

Li, Shengxu; Zhao, Jing Hua; Luan, Jian’an; Ekelund, Ulf; Luben, Robert; Khaw, Kay‐Tee; Wareham, Nicholas J.; Loos, Ruth J.F.

doi:10.1371/journal.pmed.1000332

Cited by 261 publications

(289 citation statements)

References 33 publications

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“…The prospective Norfolk study of 20 000 men and women showed physical activity to attenuate the genetic predisposition to common obesity by 40%, as estimated by the number of risk alleles carried for 12 recently identified obesity predisposing loci. 34 In the same study, the genetic risk score was positively associated with weight gain in inactive subjects, but negatively associated in physically active subjects. Similar findings in a twin study of the United States, Finnish and Danish twins lend support to the notion that physical exercise can indeed counteract the genetic predisposition to obesity; estimates of the heritability of waist circumference, percentage of body fat and BMI significantly declined in those individuals classified as having 'high' physical activity.…”

Section: Development Of Obesitymentioning

confidence: 87%

Causes and consequences of obesity: the contribution of recent twin studies

et al. 2011

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Obesity is a genetically complex disorder that produces a myriad of health problems. Most of the recognized complications of obesity are not only strongly influenced by lifestyle factors, but also present with independent genetic predispositions that are notoriously difficult to disentangle in humans. Most studies on the causes and consequences of acquired obesity are encumbered by the incomplete ability to control for genetic influences. However, utilizing a unique experiment of nature, namely monozygotic twins (MZ) discordant for obesity as 'clonal controls' of obese and non-obese individuals has enabled the fine characterization of the effects and possible antecedents of acquired obesity while controlling for the genetic background, as well as pointed to novel obesity predisposing candidate genes. This review is a distillation of the findings from more than 10 years of research done in an exceptionally well-characterized collection of MZ and dizygotic (DZ) twins, based on the Finnish Twin Cohorts. Topics covered include the nature of development of obesity from the childhood onwards, the role of exercise in modifying the genetic susceptibility, the resulting inflammatory, prediabetic and preatherosclerotic changes in whole body and adipose tissue physiology, as well as the newest insights provided by the omics revolution. Keywords: adipose tissue; inflammation; liver fat; insulin resistance; BMI; metabolic syndrome INTRODUCTION Across time people have been fascinated by monozygotic (MZ) twins and their striking similarities in appearance, behavior as well as aspects of health and disease. In mythology, twins are often described as two halves of a whole, or alternatively as polar opposite representations of good and evil. MZ twins result from the early splitting of a single zygote and thereby are identical at the level of DNA sequence (precluding somatic mutations, epigenetic modifications and other genetic changes), whereas dizygotic (DZ) twins result from two different ova being fertilized by two separate sperm and share on average 50% of their segregating genes---just as ordinary siblings in a family. Most of the early genetic research into the heritability and variance of human traits was based on measuring the differences in within-pair correlations of various phenotypic traits between pairs of MZ and DZ twins. In addition to complex, continuous phenotypes such as height, weight and aspects of personality where MZ twins exhibit a high degree of similarity, MZ twins are nearly always concordant for Mendelian genetic diseases. Studying cases where MZ twins present with differences in the manifestation (onset, severity, response to treatment, and so on) of Mendelian diseases has helped to uncover disease mutations as well as broadened the clinical spectrum of diseases previously thought to be more uniform in presentation (Reviewed by Zwijnenburg et al., 2010). 1 Recently discordant MZ twins have also been utilized in the hunt for polymorphisms contributing to complex traits such as obesity. 2 Twin studies ha...

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Section: Development Of Obesitymentioning

confidence: 87%

Causes and consequences of obesity: the contribution of recent twin studies

et al. 2011

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“…It can also reduce obesity risk especially in those with a high genetic susceptibility (108) . Indeed, the most recent study of gene-lifestyle interactions has shown that the adverse influence of sedentary behaviour (TV watching) and beneficial influence of increasing leisure-time physical activity appear to have separate influences on the genotypic propensity for obesity (109) .…”

Section: Discussionmentioning

confidence: 99%

Energy balance and obesity: a UK perspective on the gluttonyv.sloth debate

Millward

2013

Nutr. Res. Rev.

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Obesity in the UK was assumed to have developed against a population decline in physical activity, with health messages focused on diet and exercise prevention strategies. Doubly-labelled water (DLW) studies of energy expenditure have indicated the alternative scenario that the increased obesity prevalence reflects excessive food energy intake with physical activity levels unchanged. This analysis is questionable, deriving in part from a weakness of the DLW methodology in identifying changing physical activity levels within populations of increasing body weight. This has resulted in an underestimation of the reduction in physical activity in the overweight and obese, as revealed by direct studies of such behaviour. Furthermore, a close examination of food energy supply, household food purchases and individual food energy consumption since 1955, in relation to likely estimates of current intakes indicated by simple modelling of predicted energy expenditure, identifies: (a) food energy supply as markedly overestimating energy intakes; (b) individual food energy consumption as markedly underestimating energy intakes; and (c) household food purchase data as the closest match to predicted current food energy intakes. Energy intakes indicated by this latter method have fallen by between 20 to 30 %, suggesting comparable falls in physical activity. Although unequivocal evidence for a matching UK trend in falling physical activity is limited, as is evidence that obesity follows reductions in physical activity, such a link has been recently suggested in a large prospective study in adolescents. Thus, for the UK, obesity has developed within a 'move less-eat somewhat less but still too much' scenario. A focus on both diet and exercise should remain the appropriate public health policy.

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“…The advantages of physical activity were shown in a recent study, where none of the dietary approaches alone predicted weight change; however, in combination with frequent exercise, limiting portion sizes proved to be the most successful strategy for weight gain prevention. 41 Li et al 42 have shown that an obesity gene risk score, based on 12 obesity-related genes, is associated with prospectively assessed weight change, the direction of which is dependent on physical activity levels. Among sedentary subjects, risk alleles are associated with weight gain, but among physical activity subjects, the same risk alleles predict weight loss.…”

Section: Does Dieting Make You Fatmentioning

confidence: 99%

Does dieting make you fat? A twin study

et al. 2011

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Objective: To investigate whether the paradoxical weight gain associated with dieting is better related to genetic propensity to weight gain than to the weight loss episodes themselves. Subjects: Subjects included 4129 individual twins from the population-based FinnTwin16 study (90% of twins born in Finland 1975(90% of twins born in Finland -1979. Weight and height were obtained from longitudinal surveys at 16, 17, 18 and 25 years, and number of lifetime intentional weight loss (IWL) episodes of more than 5 kg at 25 years. Results: IWLs predicted accelerated weight gain and risk of overweight. The odds of becoming overweight (body mass index (BMI)X25 kg m À2 ) by 25 years were significantly greater in subjects with one (OR 1.8, 95% CI 1.3-2.6, and OR 2.7, 1.7-4.3 in males and females, respectively), or two or more (OR 2.0, 1.3-3.3, and OR 5.2, 3.2-8.6, in males and females, respectively), IWLs compared with subjects with no IWL. In MZ pairs discordant for IWL, co-twins with at least one IWL were 0.4 kg m À2 (P ¼ 0.041) heavier at 25 years than their non-dieting co-twins (no differences in baseline BMIs). In DZ pairs, co-twins with IWLs gained progressively more weight than non-dieting co-twins (BMI difference 1.7 kg m À2 at 16 years and 2.2 kg m À2 at 25 years, Po0.001). Conclusion: Our results suggest that frequent IWLs reflect susceptibility to weight gain, rendering dieters prone to future weight gain. The results from the MZ pairs discordant for IWLs suggest that dieting itself may induce a small subsequent weight gain, independent of genetic factors.

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Physical Activity Attenuates the Genetic Predisposition to Obesity in 20,000 Men and Women from EPIC-Norfolk Prospective Population Study

Abstract: Shengxu Li and colleagues use data from a large prospective observational cohort to examine the extent to which a genetic predisposition toward obesity may be modified by living a physically active lifestyle.

Cited by 261 publications

References 33 publications

Causes and consequences of obesity: the contribution of recent twin studies

Causes and consequences of obesity: the contribution of recent twin studies

Energy balance and obesity: a UK perspective on the gluttonyv.sloth debate

Does dieting make you fat? A twin study

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