Molecular mechanisms underlying metabolic setpoints

Homeostasis refers to the body’s ability to maintain internal stability in response to fluctuations of the inner and outer environment by adapting physiological processes. Many processes in our body vary around set values; set-points. Examples are blood pH, body temperature and glucose levels. In contrast other set-points seem to shift. Body weight is not set at a certain weight. It depends on what and how much we eat.

The scheme depicts a situation in which the signal indicates a level of body energy reserves lower than those required by the adipostat 'set-point' which results in regulation of food intake (+) and thermo-  genesis (-).  From: Cannon et al., 2009,Proc Nutr Soc 68:401.

That setpoints exists can be deduced form that fact that our body is protected against weight loss; even when we are overweight -or worse obese- our body likes to return to its original state. Adipose tissue is thought to play a role in this (see figure: Adipostat hypothesis for body weight control).

Therefore questions arise such as: To what extent is do we have a weight setpoint (and are we excused for getting fat)? How does diet modulate weight setpoints and what is happening with our metabolism and genes? What is the role of adipose tissue?

In this project we aim to gain insight in metabolic adaptations of the body as a result of different diets. Characterization of these metabolic changes will be performed with the help of an animal study. Physiological changes will be identified, among others, by looking at energy intake and at energy expenditure using indirect calorimetry. Molecular changes will be characterized by whole genome transcriptome analysis, Q-PCR, adipokine profiling, and analysis of biochemical parameters of energy metabolism.

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