scholarly journals Maternal Exposure to High-Fat Diet Induces Long-Term Derepressive Chromatin Marks in the Heart

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 181 ◽  
Author(s):  
Guillaume Blin ◽  
Marjorie Liand ◽  
Claire Mauduit ◽  
Hassib Chehade ◽  
Mohamed Benahmed ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Heart Development ◽  
High Fat Diet ◽  
Target Genes ◽  
Critical Role ◽  
Maternal Exposure ◽  
High Fat ◽  
Cardiac Alterations

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.

scholarly journals CD44 contributes to hyaluronan-mediated insulin resistance in skeletal muscle of high-fat-fed C57BL/6 mice

2019 ◽  
Vol 317 (6) ◽  
pp. E973-E983 ◽  
Author(s):  
Annie Hasib ◽  
Chandani K. Hennayake ◽  
Deanna P. Bracy ◽  
Aimée R. Bugler-Lamb ◽  
Louise Lantier ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
High Fat Diet ◽  
Critical Role ◽  
Chow Diet ◽  
Wild Type ◽  
High Fat ◽  
Insulin Resistant ◽  
Beneficial Effects

Extracellular matrix hyaluronan is increased in skeletal muscle of high-fat-fed insulin-resistant mice, and reduction of hyaluronan by PEGPH20 hyaluronidase ameliorates diet-induced insulin resistance (IR). CD44, the main hyaluronan receptor, is positively correlated with type 2 diabetes. This study determines the role of CD44 in skeletal muscle IR. Global CD44-deficient ( cd44−/−) mice and wild-type littermates ( cd44+/+) were fed a chow diet or 60% high-fat diet for 16 wk. High-fat-fed cd44−/− mice were also treated with PEGPH20 to evaluate its CD44-dependent action. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp (ICv). High-fat feeding increased muscle CD44 protein expression. In the absence of differences in body weight and composition, despite lower clamp insulin during ICv, the cd44−/− mice had sustained glucose infusion rate (GIR) regardless of diet. High-fat diet-induced muscle IR as evidenced by decreased muscle glucose uptake (Rg) was exhibited in cd44+/+ mice but absent in cd44−/− mice. Moreover, gastrocnemius Rg remained unchanged between genotypes on chow diet but was increased in high-fat-fed cd44−/− compared with cd44+/+ when normalized to clamp insulin concentrations. Ameliorated muscle IR in high-fat-fed cd44−/− mice was associated with increased vascularization. In contrast to previously observed increases in wild-type mice, PEGPH20 treatment in high-fat-fed cd44−/− mice did not change GIR or muscle Rg during ICv, suggesting a CD44-dependent action. In conclusion, genetic CD44 deletion improves muscle IR, and the beneficial effects of PEGPH20 are CD44-dependent. These results suggest a critical role of CD44 in promoting hyaluronan-mediated muscle IR, therefore representing a potential therapeutic target for diabetes.

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

2019 ◽  
Vol 29 ◽  
pp. S225-S226
Author(s):  
M. Mazzelli ◽  
N. Cattane ◽  
C. Mora ◽  
V. Begni ◽  
A. Berry ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
High Fat Diet ◽  
Long Term Effects ◽  
High Fat ◽  
Prenatally Stressed

scholarly journals High-Fat Diet Promotes DSS-Induced Ulcerative Colitis by Downregulated FXR Expression through the TGFB Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Di Zhao ◽  
Chenwen Cai ◽  
Qiyi Chen ◽  
Shuang Jin ◽  
Bo Yang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
High Fat Diet ◽  
Target Genes ◽  
Intestinal Inflammation ◽  
Farnesoid X Receptor ◽  
Mucosal Barrier ◽  
High Fat ◽  
Colon Rectal Cancer ◽  
Chronic Intestinal Inflammation

Ulcerative colitis is one of the IBD which cause a chronic intestinal inflammation and dysfunctional of the mucosal barrier. For now, the incident of UC was steadily increased all over the world. It has become a novel independent risk factor of several severe diseases especially colon-rectal cancer. However, the etiology of UC was still obscure. Previous studies show that high-fat diet contributed to the pathogenesis of immune system dysregulation, and farnesoid X receptor (FXR) was also implicated in the pathogenesis of various inflammatory symptoms. Yet, their inner roles in the pathogenesis of UC have not been mentioned. In this study, we aim to investigate the role of FXR in UC. High-fat diet (HFD) promotes the progression of DSS-induced UC, shows an increasing secretion of bile acid in serum, and leads to a downregulation of FXR target genes (FXRα, Shp, and lbabp). Adding FXR agonist FexD rescues the phenotype induced by high-fat diet, whereas TGFBRI inhibitor SB431542 abrogates the restoration by FexD in DSS-induced UC mice. To further verify the relationship between the FXR and TGFB signaling pathway, we made a UC-HFD model in the Caco2 cell line. Results shows the same conclusion that FXR mitigate UC inflammation through a TGFB-dependent pathway. These results expand the role of FXR in ulcerative colitis and suggest that FXR activation may be considered a therapeutic strategy for UC.

scholarly journals Long-term high-fat diet induces hippocampal microvascular insulin resistance and cognitive dysfunction

2017 ◽  
Vol 312 (2) ◽  
pp. E89-E97 ◽  
Author(s):  
Zhuo Fu ◽  
Jing Wu ◽  
Tanseli Nesil ◽  
Ming D. Li ◽  
Kevin W. Aylor ◽  
...  
Keyword(s):  
Cognitive Function ◽  
High Fat Diet ◽  
Critical Role ◽  
Capillary Density ◽  
Chow Diet ◽  
High Fat ◽  
Insulin Resistant ◽  
Old Rats ◽  
Insulin Responses

Insulin action on hippocampus improves cognitive function, and obesity and type 2 diabetes are associated with decreased cognitive function. Cerebral microvasculature plays a critical role in maintaining cerebral vitality and function by supplying nutrients, oxygen, and hormones such as insulin to cerebral parenchyma, including hippocampus. In skeletal muscle, insulin actively regulates microvascular opening and closure, and this action is impaired in the insulin-resistant states. To examine insulin’s action on hippocampal microvasculature and parenchyma and the impact of diet-induced obesity, we determined cognitive function and microvascular insulin responses, parenchyma insulin responses, and capillary density in the hippocampus in 2- and 8-mo-old rats on chow diet and 8-mo-old rats on a long-term high-fat diet (6 mo). Insulin infusion increased hippocampal microvascular perfusion in rats on chow diet by ~80–90%. High-fat diet feeding completely abolished insulin-mediated microvascular responses and protein kinase B phosphorylation but did not alter the capillary density in the hippocampus. This was associated with a significantly decreased cognitive function assessed using both the two-trial spontaneous alternation behavior test and the novel object recognition test. As the microvasculature provides the needed endothelial surface area for delivery of nutrients, oxygen, and insulin to hippocampal parenchyma, we conclude that hippocampal microvascular insulin resistance may play a critical role in the development of cognitive impairment seen in obesity and diabetes. Our results suggest that improvement in hippocampal microvascular insulin sensitivity might help improve or reverse cognitive function in the insulin-resistant states.

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

2018 ◽  
Vol 107 (2) ◽  
pp. 147-157 ◽  
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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