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Are Rodent Models Fit for Investigation of Human Obesity and Related Diseases?

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Developed countries, but also most developing areas of the world, are experiencing a high prevalence of overweight and obesity. Its complications are among the leading causes of premature mortality from conditions such as coronary heart disease, stroke, and type 2 diabetes that place a heavy burden on ...

Developed countries, but also most developing areas of the world, are experiencing a high prevalence of overweight and obesity. Its complications are among the leading causes of premature mortality from conditions such as coronary heart disease, stroke, and type 2 diabetes that place a heavy burden on healthcare systems.

Obesity develops as an interaction between genetic traits and environmental factors such as high energy density diets and sedentary behaviors. Some individuals thus are more at risk of becoming obese as a result of biological and behavioral differences entrained by a combination of many genes (thrifty genotype) or the possibility that some of the biological predisposition is associated with epigenetic events unfolding during fetal life or early postnatal periods. On the other hand, the protocols implemented to help obese people lose weight have revealed their limited efficacy, and it is now acknowledged that only a small proportion of subjects are able to maintain in the long-term the weight lost during the first weeks of regimen. The obvious conclusion is that, once established, obesity is quite impossible to reverse without lifelong severe dietary restriction usually combined with involvement in regular exercise training that most subjects are unable to continue in the long-term.

In light of these facts, it is necessary that people prone to obesity be diagnosed before they gain weight, which implies that one fundamental axis of future research should be to diagnose, in the still lean individual, the behavioral, metabolic, neurological and genetic characteristics that can predispose to body weight gain in response to various environmental situations.

Acknowledging that rodent models are not necessarily perfect experimental models to conclude about human beings, the studies performed on rats and mice spontaneously prone or resistant to obesity and on genetically engineered mice have already brought a lot of information on the metabolic defects that can pre-exist before obesity, and be responsible for an increased sensitivity to various environmental pressures such as high fat, high sucrose and even low fat diets, sedentary behavior, environmental factors during pregnancy, lactation and so on.

The goal of this topic (open to suggestions by contributors) is to get from experimental scientists reviews of the most relevant results of their own research or more general overviews of the results brought by animal studies, to discuss the various methodological approaches, to what extent the use of animal models allowed significant progress and/or proves to be of limited use to describe what really happens in humans, and to consider future strategies to best use these models to progress in the comprehension of the mechanisms making some people more sensitive than others to the pressure of the present “obesogenic” environment. It is expected that grouping 15-20 such articles in an e-book published by Frontiers will become an important reference for those involved in obesity research.


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