Abstract
ObjectiveThe prevalence of overweight and obesity among children has drastically increased during the last decades and maternal obesity has been demonstrated as one of the ultimate factors. Nutrition-stimulated transgenerational regulation of key metabolic genes is fundamental to the developmental origins of the metabolic syndrome. Fetal nutrition may differently influence female and male offspring.MethodsMice dam were fed either a control diet or a high-fat diet (HFD) for 6-week prior mating and continued their respective diet during gestation and lactation. At weaning, female and male offspring were fed the HFD until sacrifice. White (WAT) and brown (BAT) adipose tissues were investigated in vivo by nuclear magnetic resonance at two different timepoints in life (midterm and endterm) and tissues were collected at endterm for lipidomic analysis and RNA sequencing. We explored the sex-dependent metabolic adaptation and gene programming changes by maternal HFD in visceral AT (VAT), subcutaneous AT (SAT) and BAT of offspring.ResultsWe show that the triglyceride profile varies between adipose depots, sexes and maternal diet. In female offspring, maternal HFD remodels the triglycerides profile in SAT and BAT, and increases thermogenesis and cell differentiation in BAT, which may prevent metabolic complication later in life. Male offspring exhibit whitening of BAT and hyperplasia in VAT when born from high-fat mothers, with impaired metabolic profile. Maternal HFD differentially programs gene expression in WAT and BAT of female and male offspring.ConclusionMaternal HFD modulates metabolic profile in offspring in a sex-dependent manner. A sex- and maternal diet-dependent gene programming exists in VAT, SAT, and BAT which may be key player in the sexual dimorphism in the metabolic adaptation later in life.
Highlights
The drastic increase in consumption of high caloric diets worldwide with high levels of modified fat by the food industry associated with a sedentary lifestyle, has dramatically challenged humans’ metabolism
We show that stressing dams with high-fat diet (HFD) during preconception, gestation and lactation has major effects on the developmental programming of Adipose tissue (AT) in F1 offspring
These changes may determine the risk for developing metabolic complications later in life
Summary
The drastic increase in consumption of high caloric diets worldwide with high levels of modified fat by the food industry associated with a sedentary lifestyle, has dramatically challenged humans’ metabolism. Several studies have demonstrated the noteworthy sensitivity of the offspring to nutritional environment during the prenatal, neonatal and postnatal periods, which facilitates the development of metabolic complications in adulthood [2,3,4]. The intrauterine programming of obesity in offspring adulthood relies on genetic regulation as a key mechanism [5]. Genetic modifications by maternal high-fat diet (moHF) lead to a cyclical transgenerational transmission that soon may become a heavy burden worldwide. Sex-dependent metabolic adaptation to moHF has been recently described by our group and others, but the underlying mechanism remains to be elucidated [4, 6, 7]
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