The prevalence of obesity in the Nordic countries has increased from about < 1% shortly after the second world war to 15-20% today. As the gene pool has not changed the causes are entirely environmental, and due to factors such as increased food availability, low levels of physical activity, and a diet promoting passive overconsumption through a high content of fat, sugar-rich soft drinks, beer and wine.

However, there is good evidence to suggest that those becoming obese possess a genetic susceptibility that makes their energy balance more vulnerable to the environmental stimuli.

Genetic epidemiological studies have found that overweight subjects with a familial history of obesity are more likely to gain weight on a high-fat diet than those without this background.

This effect might be mediated through a preference for fat, a weaker satiating power of fat, a blunted thermogenic effect, and an impaired capacity to mobilise and oxidise fat during periods of negative energy balance.

Experimental studies in formerly obese subjects have found that their 24 h energy expenditure and fat oxidation adjust more slowly to increases in dietary fat content than matched never-obese controls, factors that are likely to contribute to the increased susceptibility to weight gain and resistance to weight loss. An impaired fat oxidation capacity in formerly obese subjects has been traced to oxidative enzyme systems in skeletal muscle, which are not explained by differences in physical activity. The genetic counterparts of these findings are unknown. However, in this context the peroxisome proliferator-activated receptor-λ (PPAR-λ) gene is interesting. This gene produces two proteins, one of which, PPAR-λ, is found in adipose tissue, where it plays a key role in the regulation of adipocyte differentiation. Activation of these receptors causes recruitment of pre-adipocyte fibroblasts to form mature cells, which then accumulate fat. The endogenous PPAR-λ ligands are fatty acids, eicosanoids and prostaglandins, which suggests the possibility that hyperplasia might be induced (and inhibited) by dietary factors, such as specific fatty acids (trans fatty acids, CLA, etc.). The importance is supported by reports that polymorphisms and mutations in the PPAR-λ gene or the encoding region of the gene have been associated with obesity and diabetes.

Single mutations in the genes encoding for the adipose tissue hormone leptin and its hypothalamic receptor exert a very powerful effect on energy balance in humans through a marked hyperphagia, which is difficult to limit unless there is a shortage of food. By contrast, genes that are expressed only when the lifestyle is sedentary, and the diet is fat and energy dense, are more likely to be operating in most obese individuals. High levels of plasma leptin, adjusted for body fat mass, are associated with resistance to weight loss during marked energy restriction, which might be an expression of hypothalamic leptin resistance or secondary to a low fat oxidation (Verdich et al. 2001).

The PPAR-λ2 gene also seems to be important for fat oxidative responsiveness during weight loss and propensity to regain weight after a diet-induced weight loss (Nicklas et al. 2001), and the Pro12Aala variant of this gene may influence the susceptibility for weight regain and obesity. Similarly, genes, and perhaps also environmental factors controlling the proton leak and uncoupling protein (UCP) expression, are important determinants of fat oxidation capacity, and influence weight loss outcome during energy restriction (Harper et al. 2002).

Ongoing and future research in genes and variants with effect on appetite regulation and metabolic efficiency during weight gain, and weight loss, should give us a better insight into body weight regulation in obesity, and perhaps make it possible to design individualised diets based on personal genetic make-up.