Effect of dietary lipid structure in early postnatal life on mouse adipose tissue development and function in adulthood

Abstract

Obese individuals have more (hyperplastic) and larger (hypertrophic) adipocytes in their white adipose tissue (WAT) than normal-weight individuals. The difference in cell number emerges early in childhood, suggesting that this is a critical period for being susceptible to obesity. Breast-feeding has been shown to be protective against obesity, and we have previously shown in mice that the physical structure of lipids in human milk may contribute to this protective effect. In the present study, we investigated how differences in the physical structure of lipids in the early diet may modulate adipose tissue development. Male mice were fed a diet containing control infant milk formula (Control IMF; Danone Research) or Nuturis w (Concept IMF with large phospholipid-coated lipid droplets; Danone Research) from postnatal day (PN)16 to 42. Subsequently, mice were challenged with a moderate Western-style diet (WSD) until PN98, and body composition was monitored by dual-energy X-ray absorptiometry. Epididymal WAT was analysed for adipocyte size, number and gene expression of metabolic transcription factors. Early Concept IMF exposure reduced fat accumulation during the WSD challenge by 30 % compared with the Control IMF. It reduced adipocyte size without affecting adipocyte number in adult mice. The Concept IMF decreased the expression of PPARg, CCAAT/enhancer-binding protein and retinoid X receptor a in WAT in adulthood, key regulators of metabolic activity. In conclusion, Concept IMF exposure in early life reduced susceptibility to obesity in adult life, by preventing adipocyte hypertrophia upon adult dietary challenge without affecting adipogenesis. These data emphasise the importance of the physical properties of dietary lipids in early life in obesity risk later in life.

A novel infant milk formula concept: Mimicking the human milk fat globule structure

“…Mice fed Concept IMF until early adulthood showed reduced adiposity when subsequently challenged by a moderately high-fat Western-style diet in adolescence and adulthood despite similar food intake [18,19]. These nutritional programming models using rodent pups [18,19] suggested that the altered lipid structure of the Concept IMF in early life affected adult adipocyte functionality but not adipocyte number. Also, the metabolic response to this diet was improved in Concept IMF-fed mice, with lower body weight and lower plasma insulin despite similar food intake.…”

Towards infant formula biomimetic of human milk structure and digestive behaviour

“…At this stage, however, the fact that kinetics of lipid digestion could further modulate plasma TG appearance (Michalski et al, 2006) and b-oxidation rate (Michalski et al, 2005a) was already established in animal models and later on confirmed in human (Vors et al, 2013). In a further study (Oosting et al, 2014), still using a very close design study in mice, it was shown (2015) and Bourlieu et al (2015a).…”

“…Several meta-analyses have shown that breast-feeding has a small protective effect against obesity later in life (Agostoni et al, 2009). Relying on these positive outcomes and considering the strong difference of lipid structure between IF and HM, Oosting et al (2014) set the hypothesis that HM lipid structure was involved in programming.…”

“…Further proofs of evidence of lipids being involved in programming other functions were obtained in 2010 in animal models (rodents) by two research groups (Innis et al, 2010;Oosting et al, 2010). These results were obtained on non-dairy lipids but paved the way for further investigations on 'dairy lipid structure and programming' conducted just after by Oosting et al (2011Oosting et al ( , 2012Oosting et al ( , 2014.…”

Milk Polar Lipids Affect In Vitro Digestive Lipolysis and Postprandial Lipid Metabolism in Mice

“…In humans, milk fat emulsified by protein results in enhanced lipemia and higher b-oxidation (i.e., lower storage) than unemulsified fat (25). There is also evidence that PLs consumed early in development may have lasting effects on metabolism, because mice pups initially fed an infant formula composed of large lipid droplets coated with MPLs were then less susceptible to the deleterious effects of a high-fat diet, compared with infant formula that contained small lipid droplets coated with proteins (26,27). Collectively, these data indicate that PLs as emulsifiers may affect postprandial lipid trafficking via a mechanism involving differential digestive hydrolysis and that the composition and character of the PLs isolated from different sources may contribute to this process.…”