Early life nutrition, altered inflammatory responsiveness and the path to programmed obesity and metabolic dysfunction

Abstract

Background: Obesity continues to be a global health concern. Accumulating evidence demonstrates that obesity and related metabolic disorders have developmental origins. Maternal obesity programs offspring to develop obesity and related cardiometabolic disorders in later life, which can perpetuate a transgenerational cycle. The surrounding mechanisms remain unclear, however low-grade metabolic inflammation has been implicated as a key underlying mechanism. Given the widespread consequences, identifying effective interventions to mitigate programmed metabolic dysfunction is of utmost importance. Aim: To investigate the mechanisms mediating the adverse metabolic outcomes in offspring as a consequence of maternal obesogenic nutrition, and to evaluate the impact of maternal supplementation with dietary agents reported to alter inflammatory processes. Methods: We utilised an established Sprague-Dawley rat model of maternal high fat feeding during pregnancy and lactation. In three separate studies, we investigated the effects of supplementation with conjugated linoleic acid (CLA), fish oil and a high amount of dietary salt. CLA and fish oil were assessed because of their reported anti-inflammatory properties. Given the relevance of high salt consumption in Western-style diets, we also assessed the impact of a high salt diet, which can have pro-inflammatory effects. Offspring metabolic profiles, adipocyte morphology and gene expression were assessed. Results: Maternal CLA supplementation to a high fat diet had a range of beneficial effects in mothers and offspring, including normalising fetal weight, pre-weaning growth trajectory, adult male offspring adiposity, insulin sensitivity and adipocyte morphology. Maternal fish oil administration to a high fat diet reduced fat mass and improved insulin sensitivity, but increased inflammatory gene expression in adult male offspring. Adult male offspring from mothers consuming a high fat and high salt diet had reduced body weight, improved insulin sensitivity and reduced gut inflammatory gene expression compared to offspring from mothers who consumed a high fat diet. Conclusions: Our studies provide further insight into the mechanisms linking altered maternal nutrition and offspring metabolic outcomes. CLA may be a promising intervention to minimise high fat diet-induced developmental programming, however fish oil and high salt diets have unanticipated effects which warrant further investigation. Our studies highlight the importance of trialling potential interventions in different maternal nutritional conditions and evaluating multiple tissues and both sexes in offspring.