Abstract
A variety of models have been developed to better understand the mechanisms underlying
individual variation in susceptibility to obesity. This review discusses several of
these models and explores their role in understanding individual vulnerability to
metabolic disease and the environmental factors around which metabolic perturbations
occur. Recently, the focus of models has shifted towards heterogeneous populations,
in which individuals characterized by a high vulnerability and individuals that are
seemingly resistant can be identified. The use of these heterogeneous studies has
lead to the identification of several novel biomarkers predicting obesity. This review
therefore focuses on nontraditional factors, which are not directly implicated in
metabolic regulation. First, the evidence from rodent knockout models for genetic
factors involved in obesity is discussed. Second, the role of a stressful environment,
particularly the early life environment is investigated along with a discussion of
circadian disruption and metabolic disorders. Finally, the impact of sex-steroids,
as exemplified by polycystic ovarian syndrome, is discussed. Overall, the data presented
in our review demonstrate that in most cases interplay between genetic and environmental
factors best predicts disease development. Our review shows that susceptibility to
obesity may be explained by complex interactions between traditional homeostatic mechanisms,
such as the hypothalamic peptide, and less studied mechanisms, like steroids and neurotrophic
factors.
Key words
polycystic ovary syndrome - glucocorticoids - obesity - neuropeptides
