Maternal high-fat diet programs white and brown adipose tissue lipidome and transcriptome in offspring in a sex- and tissue-dependent manner in mice

Abstract

Objective The 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. Methods Mice 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. Results We 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. Conclusion Maternal 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.

Maternal obesity and resistance to breast cancer treatments among offspring: Link to gut dysbiosis

“…Since TCA cycle is a key regulator of cellular metabolism, increase in VAT impairs the ability of cells to maintain optimal energy production to support their function. Savva et al have studied the impact of maternal obesity on metabolism in visceral, subcutaneous and brown adipose tissue in the offspring, and among the many changes, most of which are gender‐specific, an impaired TCA cycle and OXPHOS in female offspring 51 …”

“…Savva et al have studied the impact of maternal obesity on metabolism in visceral, subcutaneous and brown adipose tissue in the offspring, and among the many changes, most of which are gender‐specific, an impaired TCA cycle and OXPHOS in female offspring. 51 …”

The Sexual Dimorphism of Human Adipose Depots

“…In mice, a recent study demonstrates that maternal obesity impairs the thermogenesis and energy expenditure of BAT, predisposing female offspring to obesity and metabolic dysfunctions via Dio3os , a maternally imprinted long-noncoding RNA [ 79 ]. It has also been shown that maternal high-fat diet feeding before and during pregnancy affects gene expression in WAT and BAT of the offspring in a sex- and adipose-depot-dependent manner, which may prevent metabolic complications in females but not in males [ 80 ].…”

Intestinal microbiomics and liver metabolomics insights into the preventive effects of chromium (III)-enriched yeast on hyperlipidemia and hyperglycemia induced by high-fat and high-fructose diet

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