Abstract
Maternal obesity during pregnancy is associated with a greater risk of poor health outcomes in offspring, including obesity, metabolic disorders, and anxiety, however the incidence of these diseases differs for males and females. Similarly, animal models of maternal obesity have reported sex differences in offspring, for both metabolic outcomes and anxiety-like behaviors. The ventromedial nucleus of the hypothalamus (VMN) is a brain region known to be involved in the regulation of both metabolism and anxiety, and is well documented to be sexually dimorphic. As the VMN is largely composed of glutamatergic neurons, which are important for its functions in modulating metabolism and anxiety, we hypothesized that maternal obesity may alter the number of glutamatergic neurons in the offspring VMN. We used a mouse model of a maternal high-fat diet (mHFD), to examine mRNA expression of the glutamatergic neuronal marker Satb2 in the mediobasal hypothalamus of control and mHFD offspring at GD17.5. We found sex differences in Satb2 expression, with mHFD-induced upregulation of Satb2 mRNA in the mediobasal hypothalamus of female offspring, compared to controls, but not males. Using immunohistochemistry, we found an increase in the number of SATB2-positive cells in female mHFD offspring VMN, compared to controls, which was localized to the rostral region of the nucleus. These data provide evidence that maternal nutrition during gestation alters the developing VMN, possibly increasing its glutamatergic drive of offspring in a sex-specific manner, which may contribute to sexual dimorphism in offspring health outcomes later in life.
Highlights
During the prenatal period, the developing brain is vulnerable to adverse maternal nutrition.A growing body of research indicates that maternal high-fat diet (mHFD) and obesity during pregnancy can adversely impact the health of offspring throughout their lifespan, increasing the life-long risk of obesity, metabolic disorders, and cardiovascular disease [1]
We found mHFD-induced obesity led to significant upregulation of Satb2 mRNA expression in the hypothalamus of mHFD female offspring in comparison to controls, but this did not occur in mHFD males
Satb2 mRNA is Upregulated in Mediobasal Hypothalamus of GD17.5 Female Offspring from mFD-Induced
Summary
The developing brain is vulnerable to adverse maternal nutrition. Glutamatergic neurotransmission, both within the VMN and to other interconnected brain regions, is important for the numerous functions it mediates, including glucose homeostasis, metabolism, and anxiety behaviors [21,23] This led us to the hypothesis that a maternal high fat diet during gestation may disrupt glutamatergic signaling in the VMN of developing offspring in a sex specific manner. We found that Satb transcript upregulation was associated with an increased number of SATB2 immunolabelled cells residing in rostral regions of the VMN in female mHFD offspring Together, these data provide additional evidence of sex-specific vulnerability of the offspring’s brain to maternal nutrition during development, and identifies the VMN as a novel brain region that may contribute to sex-differences in the developmental programming of both obesity and anxiety
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