Putting the diet back into diet-induced obesity: diet-induced hypothalamic gene expression.
A wealth of detailed mechanistic information relating to obesity and body weight regulation has emerged from study of single gene mutation models, and continues to be generated by engineered rodent models targeting specific genes. However, as an early step in translational research, many researchers are turning to models of diet-induced obesity. Interpretation of data generated from such models is not aided by the variety of diets and rodent strains employed in these studies and a strong case could be made for rationalisation. Differences in experimental protocol, which may deploy a single obligatory solid diet, a choice of solid diets, or liquid/solid combinations, and which may or may not allow a preferred macronutrient composition to be selected, mean that different models of diet-induced obesity achieve that obesity by different routes. The priority should be to mimic the palatability- and choice-driven over-consumption that probably underlies the majority of human obesity. Some of the hypothalamic energy balance genes apparently 'recognise' developing diet-induced obesity as indicated by counter-regulatory changes in expression levels. However, substantial changes in gene expression on long-term exposure to obesogenic diets are not able to prevent weight gain. Forebrain reward systems are widely assumed to be overriding hypothalamic homeostatic energy balance systems under these circumstances. More mechanism-based research at the homeostatic/reward/diet interface may enable diets to be manipulated with therapeutic benefit, or define the contribution of these interactions to susceptibility to diet-induced obesity.
Mercer
Julian G
JG
Division of Obesity and Metabolic Health, Rowett Research Institute, Aberdeen Centre for Energy Regulation and Obesity (ACERO), Aberdeen AB21 9SB, Scotland. J.Mercer@rowett.ac.uk
Archer
Zoë A
ZA
D000818:Animals; D004032:Diet; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley