Interaction between genes and lifestyle factors on obesity

Abstract

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 singlenucleotide 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. Geneenvironment 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 PPARg2 (Pro12Ala), b-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.Obesity risk: Mutations: Physical activity: Diet: Gene-environment interaction Genetics of obesityNowadays, the availability of genomics technology represents a major advance in the study of the genetics of obesity (1,2) . Human genetic differences appear at the level of single-nucleotide polymorphisms, copy-number polymorphisms and the specific combinations of alleles (haplotypes) (3,4) . The configuration of multiple genes can range from polygenic (i.e. many genes with a relatively small contribution) to oligogenic (i.e. few genes with large measurable effects often expressed on a residual polygenic background). Indeed, it is this oligogenic architecture that has justified the current efforts to map genes for complex phenotypes. In the present paper the influence of a number of single-nucleotide polymorphisms in genes encoding factors regulating food and energy intake and factors implicated in energy expenditure and adiposity will be summarised. Genes encoding factors regulating food and energy intakeIt is generally accepted that hypothalamic and brain stem centres are involved in the regulation of food intake and energy balance but only in the last decade has information on the relevant regulatory factors and their genes ...

Usefulness of combining intermittent hypoxia and physical exercise in the treatment of obesity

“…The main etiological factors causing excess body weight for height are assigned to overeating and low physical activity, which lead to a positive energy balance, and result in a body fat increase [91]. Furthermore, there are other causes such as the genetic component, the distribution of energy intake throughout the day, the dietary composition of macronutrients, sleep rest, endocrine disruptions or the individual ability to oxidize energy substrates [26,70,93].…”

“…Furthermore, there are other causes such as the genetic component, the distribution of energy intake throughout the day, the dietary composition of macronutrients, sleep rest, endocrine disruptions or the individual ability to oxidize energy substrates [26,70,93]. Thus, obesity is a chronic multifactorial disease resulting from the interaction between genotype, environment and physical activity patterns [14,91,95].…”

“…Furthermore, there are other causes such as the genetic component, the distribution of energy intake throughout the day, the dietary composition of macronutrients, sleep rest, endocrine disruptions or the individual ability to oxidize energy substrates [26,70,93]. Thus, obesity is a chronic multifactorial disease resulting from the interaction between genotype, environment and physical activity patterns [14,91,95].Obesity is considered one of the major risk factors in the onset of associated chronic diseases, such as hypercholesterolemia, type II diabetes (T2D), cardiovascular disorders and metabolic syndrome features [101]. On the other hand, the higher BMI and waist circumference are, the greater is the relative risk of comorbidities [118].…”

Leptin and TNF-alpha promoter methylation levels measured by MSP could predict the response to a low-calorie diet

“…Up to now, obesity has been studied as a polygenic disease involving complex gene-gene and gene-environment interactions [28].…”

Lifestyle factors modify obesity risk linked to PPARG2 and FTO variants in an elderly population: a cross-sectional analysis in the SUN Project

“…Obesity is a complex disease with genetic and environmental basis (Marti et al 2008). FTO and PPARG2 gene variants for obesity risk have been widely studied (Razquin et al 2011).…”