Long-term impact of maternal high-fat diet on offspring cardiac health: role of micro-RNA biogenesis

Heart diseases are a leading cause of death. While the link between early exposure to nutritional excess and heart disease risk is clear, the molecular mechanisms involved are poorly understood. In the developmental programming field, increasing evidence is pointing out the critical role of epigenetic mechanisms. Among them, polycomb repressive complex 2 (PRC2) and DNA methylation play a critical role in heart development and pathogenesis. In this context, we aimed at evaluating the role of these epigenetic marks in the long-term cardiac alterations induced by early dietary challenge. Using a model of rats exposed to maternal high-fat diet during gestation and lactation, we evaluated cardiac alterations at adulthood. Expression levels of PRC2 components, its histone marks di- and trimethylated histone H3 (H3K27me2/3), associated histone mark (ubiquitinated histone H2A, H2AK119ub1) and target genes were measured by Western blot. Global DNA methylation level and DNA methyl transferase 3B (DNMT3B) protein levels were measured. Maternal high-fat diet decreased H3K27me3, H2Ak119ub1 and DNA methylation levels, down-regulated the enhancer of zeste homolog 2 (EZH2), and DNMT3B expression. The levels of the target genes, isl lim homeobox 1 (Isl1), six homeobox 1 (Six1) and mads box transcription enhancer factor 2, polypeptide C (Mef2c), involved in cardiac pathogenesis were up regulated. Overall, our data suggest that the programming of cardiac alterations by maternal exposure to high-fat diet involves the derepression of pro-fibrotic and pro-hypertrophic genes through the induction of EZH2 and DNMT3B deficiency.

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Long term effects of high fat diet given early in life in prenatally stressed rats: role of the inflammatory response

10.26226/morressier.5b681761b56e9b005965c755 ◽

2018 ◽

Author(s):

Mazzelli Monica ◽

Veronica Begni ◽

Marco Andrea Riva ◽

Annamaria Cattaneo

Keyword(s):

Inflammatory Response ◽

High Fat Diet ◽

Long Term Effects ◽

High Fat ◽

Prenatally Stressed

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Stress Aggravates High-Fat-Diet-Induced Insulin Resistance via a Mechanism That Involves the Amygdala and Is Associated with Changes in Neuroplasticity

Neuroendocrinology ◽

10.1159/000491018 ◽

2018 ◽

Vol 107 (2) ◽

pp. 147-157 ◽

Cited By ~ 3

Author(s):

Sheng-Feng Tsai ◽

Hung-Tsung Wu ◽

Pei-Chun Chen ◽

Yun-Wen Chen ◽

Megan Yu ◽

...

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

Tissue Expansion ◽

Plasma Corticosterone ◽

High Fat ◽

Obesity In Mice ◽

Bilateral Lesions

Background: The notion that exposure to chronic stress predisposes individuals to developing type 2 diabetes (T2D) has gained much attention in recent decades. Long-term stress induces neuroadaptation in the amygdala and increases corticosterone levels. Corticosterone, the major stress hormone in rodents, induces insulin resistance and obesity in mice. However, little is known about whether the stress-induced amygdalar neuroadaptation could promote the risk of T2D. Methods: We used an 11-week high-fat diet (HFD) feeding paradigm to induce insulin dysfunction in mice, followed by implementation of a 10-day social defeat (SD) stress protocol. Results: Mice receiving SD at the beginning of the HFD feeding aggravated HFD-induced insulin resistance and white adipose tissue expansion. HFD mice had higher levels of plasma corticosterone, which was not affected by the SD. The SD stress upregulated the expression of TrkB and synaptotagmin-4 in the amygdala of HFD mice. Bilateral lesions of the central amygdalae before SD stress inhibited the stress-induced aggravating effect without affecting the HFD-induced elevation of plasma corticosterone. Conclusions: Stress aggravates HFD-induced insulin resistance and neuroadaptation in the amygdala. The HFD-induced insulin resistance is amygdala-dependent. Understanding the role of stress-induced amygdalar adaptation in the development of T2D could inform therapies aimed at reducing chronic stressors to decrease the risk for T2D.

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