Abstract
Presently, control of body weight is assumed to exist, but there is no consensus framework of body weight homeostasis. Three different models have been proposed, with a “set point” suggesting (i) a more or less tight and (ii) symmetric or asymmetric biological control of body weight resulting from feedback loops from peripheral organs and tissues (e.g. leptin secreted from adipose tissue) to a central control system within the hypothalamus. Alternatively, a “settling point” rather than a set point reflects metabolic adaptations to energy imbalance without any need for feedback control. Finally, the “dual intervention point” model combines both paradigms with two set points and a settling point between them. In humans, observational studies on large populations do not provide consistent evidence for a biological control of body weight, which, if it exists, may be overridden by the influences of the obesogenic environment and culture on personal behavior and experiences. To re-address the issue of body weight homeostasis, there is a need for targeted protocols based on sound concepts, e.g. lean rather than overweight subjects should be investigated before, during, and after weight loss and weight regain. In addition, improved methods and a multi-level–multi-systemic approach are needed to address the associations (i) between masses of individual body components and (ii) between masses and metabolic functions in the contexts of neurohumoral control and systemic effects. In the future, simplifications and the use of crude and non-biological phenotypes (i.e. body mass index and waist circumference) should be avoided. Since changes in body weight follow the mismatch between tightly controlled energy expenditure at loosely controlled energy intake, control (or even a set point) is more likely to be about energy expenditure rather than about body weight itself.
Highlights
For decades of research, body weight control has been taken as given and scientists have looked at different aspects of a proposed biological control system including genes, neuropeptides, hormones, proteins, and metabolites
Conceptual framework The conceptual framework of a biological control of body weight is mainly based on animal studies
After withdrawing that diet and introducing a mixed diet again, rats spontaneously returned to the weight of continuously mixed-diet-fed control rats[2]
Summary
Body weight control has been taken as given and scientists have looked at different aspects of a proposed biological control system including genes, neuropeptides, hormones, proteins, and metabolites. A self-critical view at the end The ideas presented in this paper point to the need for a self-critical view: two generations of scientists might have gone the wrong way when they (i) followed a hypothetical concept (i.e. there is biological control of body weight), (ii) had to accept the limited promise of methodologies to assess EB, and (iii) focused too much on statistical associations (e.g. calculating heritability estimates of BMI and, in the case of GWAS, studying associations between allele frequencies and crude anthropometric phenotypes) without addressing detailed and sound concepts and targeted analyses of structures and different levels of body weight control. Grant information The author(s) declared that no grants were involved in supporting this work
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