Developmental gene×environment interactions affecting systems regulating energy homeostasis and obesity

Abstract

Most human obesity is inherited as a polygenic trait which is largely refractory to medical therapy because obese individuals avidly defend their elevated body weight set-point. This set-point is mediated by an integrated neural network that controls energy homeostasis. Epidemiological studies suggest that perinatal and pre-pubertal environmental factors can promote offspring obesity. Rodent studies demonstrate the important interactions between genetic predisposition and environmental factors in promoting obesity. This review covers issues of development and function of neural systems involved in the regulation of energy homeostasis and the roles of leptin and insulin in these processes, the ways in which interventions at various phases from gestation, lactation and prepubertal stages of development can favorably and unfavorably alter the development of obesity n offspring. These studies suggest that early identification of obesityprone humans and of the factors that can prevent them from becoming obese could provide an effective strategy for preventing the world wide epidemic of obesity.

Replication of Obesity and Associated Signaling Pathways Through Transfer of Microbiota From Obese-Prone Rats

“…These early studies investigated the effect of gut microbiota using genetic, transgenic, or HF-fed models of obesity, none of which are an accurate reflection of human obesity that encompasses the interaction between genes and the environment (3,4,9,10). Therefore, in the current study, we examined the role of the gut microbiota in obese-prone (OP) and obese-resistant (OR) rats, a model that closely mimics the characteristics of the human obese phenotype, including a polygenic mode of inheritance, whereby some, but not all, individuals are susceptible to weight gain when exposed to an obesogenic environment (10). First, by using both chow-and HF-fed OP and OR rats, we determined whether microbiota shifts solely result from consumption of an obesogenic diet or are a manifestation of the obese phenotype.…”

Maternal touch and feed as critical regulators of behavioral and stress responses in the offspring

“…We have demonstrated that increasing dietary fat in the maternal diet blunts HPA axis activity in the shortterm, allowing critical maturational processes to occur. Additional work from our laboratory and that of others (Dunn & Bale, 2009;Levin, 2010) now demonstrates that the influences of the maternal diet, and its potential consequences on the mother-infant interactions during the preweaning period extend well beyond the neonatal period and could even span two generations. Maternal diet leads to changes in metabolic and behavioral regulation in adults and the result of gene  maternal diet interaction could modify susceptibility for cardiovascular diseases, obesity and drug-related pathologies.…”

The modulatory role of high fat feeding on gastrointestinal signals in obesity

“…The emergence of transgenic models using targeted EEC fluorescence markers have been useful in designing single-cell functional studies that resolved some of the limitations mentioned with cell lines, however, the specificity of the effects within this transgenic "modified" system and their replication in humans is still not clear. Future studies should utilize animal models that share phenotypic and metabolic characteristics of human obesity [261], and are useful in studying the interaction between HF feeding and obesity [103].…”