Energy metabolism, fuel selection and body weight regulation

Abstract

Energy homeostasis is critical for the survival of species. Therefore, multiple and complex mechanisms have evolved to regulate energy intake and expenditure to maintain body weight. For weight maintenance, not only does energy intake have to match energy expenditure, but also macronutrient intake must balance macronutrient oxidation. However, this equilibrium seems to be particularly difficult to achieve in individuals with low fat oxidation, low energy expenditure, low sympathetic activity or low levels of spontaneous physical activity, as in addition to excess energy intake, all of these factors explain the tendency of some people to gain weight. Additionally, large variability in weight change is observed when energy surplus is imposed experimentally or spontaneously. Clearly, the data suggest a strong genetic influence on body weight regulation implying a normal physiology in an 'obesogenic' environment. In this study, we also review evidence that carbohydrate balance may represent the potential signal that regulates energy homeostasis by impacting energy intake and body weight. Because of the small storage capacity for carbohydrate and its importance for metabolism in many tissues and organs, carbohydrate balance must be maintained at a given level. This drive for balance may in turn cause increased energy intake when consuming a diet high in fat and low in carbohydrate. If sustained over time, such an increase in energy intake cannot be detected by available methods, but may cause meaningful increases in body weight. The concept of metabolic flexibility and its impact on body weight regulation is also presented.

Figure 1

This figure depicts the potential effect of genes and environment on adiposity assessed by body mass index (BMI). Some of the concepts described in this figure were recently proposed by Bouchard. Our environment has evolved over the past century from a ‘traditional’ environment to a new ‘westernized’ environment. On the left part of the figure is presented the ‘traditional’ environment in which food was rather scarce and energy expenditure was high, mostly related to occupational physical activity. Such an environment leads to ‘leptogenic’ behaviors in which the variability of BMI will be dependent on the genetic propensity to weight gain of individuals. On the right part of the figure, the more recent modern ‘social’ and ‘built’ environment leads to obesogenic behaviors characterized by plenty of cheap high-calorie density food and little need for physical activity. Similarly, the variability in BMI will also depend on the genetic propensity to weight gain of individuals. Compared with the ‘obesogenic’ environment, the distribution of BMI will have a higher mean and higher standard deviation than that in the ‘leptogenic’ environment. Such a paradigm can be applied to populations with similar genetic background living in drastically different environment like the Pima Indians in Arizona and in Mexico.

Figure 2

The major components of body weight regulation in an obesogenic environment are described in this figure. Body weight in adulthood is most likely to be the result of two key components; (a) changes in the environment of subsequent generations that influence genetic and epigenetic propensity for weight gain, and (b) the current habitual lifestyle that promotes sedentary behaviors and provides an oversupply of energy dense foods. The daily energy and nutrient balance of a 70-kg man (20% body fat) in relationship to macronutrient energy stores, intake and oxidation. Each macronutrient intake and oxidation on a 2500 kcal day⁻¹ standard American diet (composition 40% fat, 40% carbohydrate and 20% protein) is shown on the left as absolute intake in kilocalories and on the right as a percentage of its respective nutrient store. Because carbohydrate, protein and alcohol intakes and oxidation rates are tightly regulated on a daily basis, any inherent differences between energy intake and energy expenditure therefore predominantly impact body fat stores. During overfeeding (shown in red), the oxidation of carbohydrate and protein is increased to compensate for the increased intake at the expense of fat intake, yet the increase in oxidation is not equally coupled with intake. Thus, if sustained fat kilocalories are stored, fat stores will expand and the body weight is gained.

Figure 3

Studies of monozygotic twins reared apart indicate that approximately one-third of the variability in body mass index (BMI) is attributable to nongenetic factors and two-thirds to genetic factors. In this figure, we broke down the genetic part of the variability in BMI into the effects of metabolic rate (MR), respiratory quotient (RQ), spontaneous physical activity (SPA; fidgeting) and sympathetic nervous activity (SNA). The remaining genetic variability is assumed to be related to the variability in food intake and physical activity. Values for MR, RQ, SPA and SNA were calculated from prospective studies conducted among the Pima Indians of Arizona.