de Vega, W. C. | Search bioRxiv

bioRxiv2020

Maternal high fat diet alters lactation-specific miRNA expression and programs the DNA methylome in the amygdala of female offspring

Adverse maternal diets high in saturated fats are associated with impaired neurodevelopment and epigenetic modifications in offspring. Maternal milk, the primary source of early life nutrition in mammals, contains lactation-specific microRNAs (miRNAs). Lactation-specific miRNAs have been found in various offspring tissues in early life, including the brain. We examined the effects of maternal high saturated fat diet (mHFD) on lactation-specific miRNAs that inhibit DNA methyltransferases (DNMTs), enzymes that catalyze DNA methylation modifications, in the amygdala of female offspring during early life and adulthood. Offspring exposed to mHFD showed reduced miR-148/152 and miR-21 transcripts in stomach milk and amygdala in the first week of life. This was associated with increased DNMT1 expression, DNMT activity, and global DNA methylation in the amygdala. In addition, persistent DNA methylation modifications from early life to adulthood were observed in pathways involved in neurodevelopment as well as genes regulating the DNMT machinery and protein function in mHFD offspring. The findings indicate a novel link between exogenous, lactation-specific miRNAs and developmental programming of the neural DNA methylome in offspring.

molecular biology↗

bioRxiv2019

Maternal high-fat diet induces sex-specific effects on inflammatory responses to corticosterone and lipopolysaccharide challenge in adult rat offspring

BackgroundAcute elevations in endogenous corticosterone (CORT) with psychosocial stress or exogenous administration potentiate inflammatory gene expression. Maternal obesity as a result of high-fat diet (HFD) consumption has been linked to higher basal levels of neuroinflammation, including increased expression of pro-inflammatory genes in the amygdala. These findings suggest that exposure to maternal HFD may elicit pro-inflammatory responses in the presence of an immune stressor such as lipopolysaccharide (LPS), a component of gram-negative bacteria, as well as acute elevated CORT. MethodsRat offspring were exposed to maternal HFD or control diet (CHD) throughout pre and postnatal development until weaning, when all offspring were provided CHD until adulthood. In adulthood, offspring were challenged with administration of exogenous CORT, to simulate an acute physiological stress, LPS, to induce an immune stress, or both. qPCR was used to measure transcript abundance of CORT receptors and downstream inflammatory genes in the amygdala, hippocampus and prefrontal cortex, brain regions that mediate neuroendocrine and behavioral responses to stress. ResultsHFD female offspring exhibited elevations in anti-inflammatory transcripts, whereas HFD male offspring responded with greater pro-inflammatory gene expression to simultaneous CORT and LPS administration. ConclusionsThese findings suggest that exposure to maternal HFD leads to sex-specific alterations that may alter inflammatory responses in the brain, possibly as an adaptive response to basal inflammation.

neuroscience↗