scholarly journals Western and Heart Healthy Dietary Patterns Differentially Affect the Expression of Genes Associated with Lipid Metabolism, Interferon Signaling and Inflammation in the Jejunum of Ossabaw Pigs

Author(s):  
Shumao Ye ◽  
Nirupa R. Matthan ◽  
Stefania Lamon-Fava ◽  
Gloria Solano Aguilar ◽  
Jerrold R. Turner ◽  
...  
2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 577-577
Author(s):  
Shumao Ye ◽  
Nirupa Matthan ◽  
Stefania Lamon-Fava ◽  
Gloria Solano-Aguilar ◽  
Jerrold Turner ◽  
...  

Abstract Objectives A gastrointestinal tract (GI) that allows for bacterial translocation has been associated with enhanced systemic inflammation and may play a critical role in the development of coronary artery disease (CAD). Diet quality and statin therapy are established modulators of CAD, but their effect in GI health is relatively unexplored. Jejunal mucosa gene expression was compared in Ossabaw pigs fed a heart healthy-type diet (HHD) and Western-type diet (WD), with and without statin therapy. Methods Pigs (N = 32) were randomized into 4 groups and fed isocalorically for 6 months: WD (high in saturated fat, refined carbohydrate, cholesterol, and low in fiber) or HHD (high in unsaturated fat, whole grains, fruits and vegetables, fiber, supplemented with fish oil, and low in cholesterol), with or without statin therapy. RNA sequencing was conducted in isolated jejunal mucosa at the end of the study. Principal component analysis, hierarchical clustering and xCell analysis were used to cross-check and ensure consistent sampling. Two-factor edgeR analysis and Ingenuity Pathway Analysis were used to identify genes, pathways, and biological functions altered by diet and/or statin. Independent of groups, Spearman's correlation coefficients were calculated to identify associations between genes of interest and atherosclerotic lesion severity in the coronary arteries or cardiometabolic risk factors (serum triglyceride, LDL, HDL, TNF-α, hsCRP). Results HHD and WD resulted in differential expression of genes related to lipid metabolism (SCD, FADS1, SQLE) in the jejunal mucosa. The expression of these genes was associated with atherosclerotic lesion severity and serum lipoprotein concentrations. Higher interferon signaling and inflammation were observed in pigs fed WD versus HHD. In the jejunal mucosa, 7 genes related to inflammation were significantly associated with serum TNF-α and/or hsCRP concentrations. There was no significant effect of statin on gene expression, nor diet x statin interaction. Expression of genes related to jejunum permeability was unaffected by diet or statin. Conclusions Gene expression in the jejunum of Ossabaw pigs was altered by dietary patterns, but not statin, and linked to atherosclerotic lesion severity associated with lipid metabolism and inflammatory markers. Funding Sources USDA-ARS-NEA, JM-USDA-HNRCA, and Tufts University.


2021 ◽  
Vol 22 (5) ◽  
pp. 2529
Author(s):  
Amin Javadifar ◽  
Sahar Rastgoo ◽  
Maciej Banach ◽  
Tannaz Jamialahmadi ◽  
Thomas P. Johnston ◽  
...  

Atherosclerosis is a major cause of human cardiovascular disease, which is the leading cause of mortality around the world. Various physiological and pathological processes are involved, including chronic inflammation, dysregulation of lipid metabolism, development of an environment characterized by oxidative stress and improper immune responses. Accordingly, the expansion of novel targets for the treatment of atherosclerosis is necessary. In this study, we focus on the role of foam cells in the development of atherosclerosis. The specific therapeutic goals associated with each stage in the formation of foam cells and the development of atherosclerosis will be considered. Processing and metabolism of cholesterol in the macrophage is one of the main steps in foam cell formation. Cholesterol processing involves lipid uptake, cholesterol esterification and cholesterol efflux, which ultimately leads to cholesterol equilibrium in the macrophage. Recently, many preclinical studies have appeared concerning the role of non-encoding RNAs in the formation of atherosclerotic lesions. Non-encoding RNAs, especially microRNAs, are considered regulators of lipid metabolism by affecting the expression of genes involved in the uptake (e.g., CD36 and LOX1) esterification (ACAT1) and efflux (ABCA1, ABCG1) of cholesterol. They are also able to regulate inflammatory pathways, produce cytokines and mediate foam cell apoptosis. We have reviewed important preclinical evidence of their therapeutic targeting in atherosclerosis, with a special focus on foam cell formation.


2021 ◽  
Author(s):  
Junli Feng ◽  
Gongshuai Song ◽  
Yuanyuan Wu ◽  
Xi Chen ◽  
Jie Pang ◽  
...  

Plasmalogens (PLs) are critical to human health. Studies have reported a link between downregulation of PLs levels and cognitive impairments in patients with Alzheimer´s disease (AD). however, the underlying mechanisms...


2018 ◽  
Vol 50 (1) ◽  
pp. 162-172 ◽  
Author(s):  
Luis D. Jiménez‐Martínez ◽  
Carlos A. Álvarez‐González ◽  
Erick De la Cruz‐Hernández ◽  
Dariel Tovar‐Ramírez ◽  
Mario A. Galaviz ◽  
...  

PLoS ONE ◽  
2017 ◽  
Vol 12 (12) ◽  
pp. e0189619 ◽  
Author(s):  
Marisa Silva Bastos ◽  
Ana Paula Del Vesco ◽  
Thaís Pacheco Santana ◽  
Thailine Santana Santos ◽  
Gregório Murilo de Oliveira Junior ◽  
...  

2019 ◽  
Vol 25 (5) ◽  
pp. 1050-1067 ◽  
Author(s):  
Hila Ben-Yehuda ◽  
Orit Matcovitch-Natan ◽  
Alexander Kertser ◽  
Amit Spinrad ◽  
Marco Prinz ◽  
...  

AbstractViral infection during pregnancy is often associated with neuropsychiatric conditions. In mice, exposure of pregnant dams to the viral mimetic poly(I:C), serves as a model that simulates such pathology in the offspring, through a process known as Maternal Immune Activation (MIA). To investigate the mechanism of such effect, we hypothesized that maternal upregulation of Type-I interferon (IFN-I), as part of the dam’s antiviral response, might contribute to the damage imposed on the offspring. Using mRNA sequencing and flow cytometry analyses we found that poly(I:C) treatment during pregnancy caused reduced expression of genes related to proliferation and cell cycle in the offspring’s microglia relative to controls. This was found to be associated with an IFN-I signature in the embryonic yolk sac, the origin of microglia in development. Neutralizing IFN-I signaling in dams attenuated the effect of MIA on the newborn’s microglia, while systemic maternal administration of IFNβ was sufficient to mimic the effect of poly(I:C), and led to increased vulnerability of offspring’s microglia to subsequent stress. Furthermore, maternal elevation of IFNβ resulted in behavioral manifestations reminiscent of neuropsychiatric disorders. In addition, by adopting a “two-hit” experimental paradigm, we show a higher sensitivity of the offspring to postnatal stress subsequent to the maternal IFNβ elevation, demonstrated by behavioral irregularities. Our results suggest that maternal upregulation of IFN-I, in response to MIA, interferes with the offspring’s programmed microglial developmental cascade, increases their susceptibility to postnatal stress, and leads to behavioral abnormalities.


2020 ◽  
Vol 11 (10) ◽  
pp. 8852-8865
Author(s):  
Jinxin Liu ◽  
Yan Li ◽  
Lamei Xue ◽  
Mingcong Fan ◽  
Chenzhipeng Nie ◽  
...  

Circulating miR-27a-3p was involved in the process of lipid synthesis under the dietary patterns of whole grain diets, and the expression of miR-27a-3p was decreased in serum, while it was elevated both in liver and ileum.


2018 ◽  
Vol 18 (6) ◽  
pp. 484-493 ◽  
Author(s):  
Xiang Cheng ◽  
Jianying Li ◽  
Deliang Guo

Lipid metabolism reprogramming emerges as a new hallmark of malignancies. Sterol regulatory element-binding proteins (SREBPs), which are central players in lipid metabolism, are endoplasmic reticulum (ER)-bound transcription factors that control the expression of genes important for lipid synthesis and uptake. Their transcriptional activation requires binding to SREBP cleavageactivating protein (SCAP) to translocate their inactive precursors from the ER to the Golgi to undergo cleavage and subsequent nucleus translocation of their NH2-terminal forms. Recent studies have revealed that SREBPs are markedly upregulated in human cancers, providing the mechanistic link between lipid metabolism alterations and malignancies. Pharmacological or genetic inhibition of SCAP or SREBPs significantly suppresses tumor growth in various cancer models, demonstrating that SCAP/SREBPs could serve as promising metabolic targets for cancer therapy. In this review, we will summarize recent progress in our understanding of the underlying molecular mechanisms regulating SCAP/SREBPs and lipid metabolism in malignancies, discuss new findings about SREBP trafficking, which requires SCAP N-glycosylation, and introduce a newly identified microRNA-29-mediated negative feedback regulation of the SCAP/SREBP pathway. Moreover, we will review recently developed inhibitors targeting the SCAP/SREBP pathway for cancer treatment.


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