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Interaction between genes and lifestyle factors on obesity: Nutrition Society Silver Medal Lecture

  • Amelia Marti (a1), Miguel Angel Martinez-González (a1) and J. Alfredo Martinez (a1)

Obesity originates from a failure of the body-weight control systems, which may be affected by changing environmental influences. Basically, the obesity risk depends on two important mutually-interacting factors: (1) genetic variants (single-nucleotide polymorphisms, haplotypes); (2) exposure to environmental risks (diet, physical activity etc.). Common single-nucleotide polymorphisms at candidate genes for obesity may act as effect modifiers for environmental factors. More than 127 candidate genes for obesity have been reported and there is evidence to support the role of twenty-two genes in at least five different populations. Gene–environment interactions imply that the synergy between genotype and environment deviates from either the additive or multiplicative effect (the underlying model needs to be specified to appraise the nature of the interaction). Unravelling the details of these interactions is a complex task. Emphasis should be placed on the accuracy of the assessment methods for both genotype and lifestyle factors. Appropriate study design (sample size) is crucial in avoiding false positives and ensuring that studies have enough power to detect significant interactions, the ideal design being a nested case–control study within a cohort. A growing number of studies are examining the influence of gene–environmental interactions on obesity in either epidemiological observational or intervention studies. Positive evidence has been obtained for genes involved in adiposity, lipid metabolism or energy regulation such as PPARγ2 (Pro12Ala), β-adrenoceptor 2 (Gln27Glu) or uncoupling proteins 1, 2 and 3. Variants on other genes relating to appetite regulation such as melanocortin and leptin receptors have also been investigated. Examples of some recently-identified interactions are discussed.

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Corresponding author
*Corresponding author: Dr Amelia Marti, fax +34 948 425649, email
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27. MC Ochoa , A Marti , C Azcona , M Chueca , M Oyarzábal , R Pelach , A Patiño , MJ Moreno-Aliaga , MA Martínez-González & JA Martínez (2004) Gene-gene interaction between PPARgamma2 and ADRbeta3 increases obesity risk in children and adolescents. Int J Obes Relat Metab Disord 28, S37S41.

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31. E Larrarte , FJ Novo , A Marti & JA Martínez (2002) UCP1 Muscle gene transfer and mitochondrial proton leak mediated thermogenesis. Arch Biophys Biochem 404, 166171.

32. A Marti , J Vaquerizo , MA Zulet , MJ Moreno-Aliaga & JA Martínez (2002) Down-regulation of heart H-FABP and UCP2 gene expressions in diet-induced (cafeteria) obese rats. J Physiol Biochem 58, 6974.

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36. A Alonso , A Martí , MS Corbalán , MA Martínez-González & JA Martínez (2005) Association of UCP3 gene –55C>T polymorphism and obesity in a Spanish population: a case-control study. Ann Nutr Metab 49, 183188.

37. J Margareto , A Marti & JA Martínez (2001) Changes in UCP mRNA expression levels in brown adipose tissue and skeletal muscle after feeding a high-energy diet and relationships with leptin, glucose and PPARG2. J Nutr Biochem 12, 130137.

38. I López , A Marti , F Milagro , MA Zulet , MJ Moreno-Aliaga & JA Martínez (2003) DNA microarray analysis of gene differentially expressed in diet-induced obese rats. Obes Res 11, 188194.

39. A Marti , MS Corbalán , MA Martínez-González , L Forga & JA Martínez (2002) CHO intake alters obesity risk associated with Pro12Ala polymorphism of PPARG gene. J Physiol Biochem 58, 219220.

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51. MC Ochoa , MJ Moreno-Aliaga , MA Martínez-González , JA Martínez , GENOI & A Marti (2006) TV watching modifies obesity risk linked to the Gln27Glu polymorphism of ADRB2 gene in girls. Int J Ped Obes 1, 8388.

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