Set points, settling points and some alternative models: theoretical options to understand how genes and environments combine to regulate body adiposity

Abstract

The close correspondence between energy intake and expenditure over prolonged time periods, coupled with an apparent protection of the level of body adiposity in the face of perturbations of energy balance, has led to the idea that body fatness is regulated via mechanisms that control intake and energy expenditure. Two models have dominated the discussion of how this regulation might take place. The set point model is rooted in physiology, genetics and molecular biology, and suggests that there is an active feedback mechanism linking adipose tissue (stored energy) to intake and expenditure via a set point, presumably encoded in the brain. This model is consistent with many of the biological aspects of energy balance, but struggles to explain the many significant environmental and social influences on obesity, food intake and physical activity. More importantly, the set point model does not effectively explain the ‘obesity epidemic’ – the large increase in body weight and adiposity of a large proportion of individuals in many countries since the 1980s. An alternative model, called the settling point model, is based on the idea that there is passive feedback between the size of the body stores and aspects of expenditure. This model accommodates many of the social and environmental characteristics of energy balance, but struggles to explain some of the biological and genetic aspects. The shortcomings of these two models reflect their failure to address the gene-by-environment interactions that dominate the regulation of body weight. We discuss two additional models – the general intake model and the dual intervention point model – that address this issue and might offer better ways to understand how body fatness is controlled.

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

“…In the large meta-analysis of GWAS, thus far performed with 123,865 individuals of European ancestry, the FTO locus was confirmed as one of the 32 variants associated with BMI with p-values \5 9 10 -8 (Speliotes et al 2010;Speakman et al 2011). A significant association between rs9939609 SNP of FTO gene and obesity, with an overall odds ratio (OR) for obesity of 1.31 under per-allele comparison, was reported in another meta-analysis including 111,571 subjects (Peng et al 2011).…”

The Role of Energy Flux in Weight Management

“…maintenance of body weight), it has been shown that EE and EI do not match on a daily basis [12][13][14]. Small differences between EI and EE, however, can have significant effects on body weight in the longterm [15]. In fact a commonly observed annual weight gain between 0.5 and 1 kg per year has been associated with an energy surplus of only 50 to 100 kcal/day [16].…”

Food-induced brain responses and eating behaviour

“…Related relevant research topics that have received relatively little or no attention in human nutritional neuroscience are nutrient sensing, dietary learning and the regulation of body adiposity (see (120) ). In the next 20 years, nutritional neuroscience will have to prove its potential for providing insights that can be used to tackle detrimental eating behaviour.…”