However, recent studies suggest that genetics contributes to 40-70% of obesity with the discovery of more than 50 genes that are strongly associated with obesity. Work on gene-environment interactions related to obesity is still in its infancy. So far, evidence suggests that genetic predisposition is not destiny: many people carrying so-called "obesity genes" do not become overweight. Rather, it appears that eating a healthy diet and getting enough exercise may offset some of the gene-related risk of obesity.
The strength of genetic influence on weight disorders varies widely from person to person. Research suggests that, for some people, genes account for only 25 per cent of the predisposition to being overweight, while for others the genetic influence is between 70 and 80 per cent. Having a rough idea of the importance of genes in your weight can be helpful in dealing with your weight problems. The arcuate nucleus of the hypothalamus comprises two sets of neurons with opposing effects on food intake and energy balance.
Activation of agouti-related peptide (AgRP) and neuropeptide Y (NPY) neurons increases food intake, while activation of proopiomelanocortin (POMC) and cocaine- and amphetamine-related transcript neurons triggers the release of alpha-melanocyte-stimulating hormone (αMSH), which binds to the melanocortin 4 receptor (MC4R) in the paraventricular nucleus to inhibit food intake and increase energy expenditure. Leptin production by fat cells is proportional to fat cell mass. Leptin signals the arcuate nucleus of the hypothalamus to down-regulate (-) the orexigenic neurons NPY and AgRP, and to up-regulate (-) the appetite-suppressing neurons POMC. In addition, two GWAS have focused on persistent healthy leanness, assuming that genes that determine resistance to weight gain may also inform obesity prevention and weight loss maintenance53,54. The widespread use of hoovers, dishwashers, leaf blowers and a host of other household appliances takes almost all the physical effort out of daily chores and may contribute as one of the causes of obesity.
The percentage of obesity that can be attributed to genetics varies widely, depending on the population examined, ranging from 6% to 85%. Most studies to date have focused on anthropometric measures of obesity (e.g. BMI, CW, HR) because they are simple, non-invasive and inexpensive surrogate measures of adiposity. A severe, early-onset form of obesity caused by a single gene mutation, with little or no environmental influence.
Although most of the current understanding of the underlying biology has been derived from monogenic forms of obesity, several successful variant-to-function translations have been performed in recent years for polygenic forms of obesity. To determine the role of other types of variation in obesity, alternative genome-wide screens have been performed. Although the rate of increase in obesity appears to be decreasing in most high-income countries, it continues to increase in many low- and middle-income countries, and prevalence remains high worldwide.8 A deletion in the canine POMC gene is associated with weight and appetite in obesity-prone Labrador retrievers. Several candidate genes for obesity have been identified (5, , and the importance of some of them has been confirmed in genetically modified mice.
The second obesity-associated gene variant the researchers identified is located on chromosome 18, near the melanocortin-4 receptor gene (the same gene responsible for a rare form of monogenic obesity). This suggests that mechanisms similar to those in monogenic forms of obesity would be involved in the common forms. One of the best known forms of syndromic obesity is Prader-Willi syndrome (PWS), caused by a chromosomal abnormality of a region imprinted on chromosome 15q11-q12.
