Endoplasmic reticulum stress epigenetics is related to adiposity, dyslipidemia, and insulin resistance

Ramos-López, Omar; Riezu-Boj, José Ignacio; Milagro, Fermı́n I.; Moreno-Aliaga, María J.; Martínéz, J. Alfredo; Mena,

doi:10.1080/21623945.2018.1447731

Cited by 19 publications

(16 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reduced global DNA methylation was noted in DNA of blood mononuclear cells from hypertensive patients, while levels of DNA hydroxymethylation appeared to respond to variable salt intake in experimental hypertension models [12]. In addition, DNA and histone methylation of endoplasmic reticulum stress genes are linked to adiposity, dyslipidemia, and insulin resistance [13].…”

Section: Introductionmentioning

confidence: 99%

Global epigenetic alterations of mesenchymal stem cells in obesity: the role of vitamin C reprogramming

et al. 2020

View full text Add to dashboard Cite

Obesity promotes dysfunction and impairs the reparative capacity of mesenchymal stem/stromal cells (MSCs), and alters their transcription, protein content, and paracrine function. Whether these adverse effects are mediated by chromatin-modifying epigenetic changes remains unclear. We tested the hypothesis that obesity imposes global DNA hydroxymethylation and histone trimethylation alterations in obese swine abdominal adipose tissue-derived MSCs compared to lean pig MSCs. MSCs from female lean (n = 7) and high-fat-diet fed obese (n = 7) domestic pigs were assessed using global epigenetic assays, before and after in-vitro co-incubation with the epigenetic modulator vitamin-C (VIT-C) (50 μg/ml). Dot blotting was used to measure across the whole genome 5-hydroxyemthycytosine (5hmC) residues, and Western blotting to quantify in genomic histone-3 protein tri-methylated lysine-4 (H3K4me3), lysine-9 (H3K9me3), and lysine-27 (H3K27me3) residues. MSC migration and proliferation were studied in-vitro. Obese MSCs displayed reduced global 5hmC and H3K4m3 levels, but comparable H3K9me3 and H3K27me3, compared to lean MSCs. Global 5hmC, H3K4me3, and HK9me3 marks correlated with MSC migration and reduced proliferation, as well as clinical and metabolic characteristics of obesity. Co-incubation of obese MSCs with VIT-C enhanced 5hmC marks, and reduced their global levels of H3K9me3 and H3K27me3. Contrarily, VIT-C did not affect 5hmC, and decreased H3K4me3 in lean MSCs. Obesity induces global genomic epigenetic alterations in swine MSCs, involving primarily genomic transcriptional repression, which are associated with MSC function and clinical features of obesity. Some of these alterations might be reversible using the epigenetic modulator VIT-C, suggesting epigenetic modifications as therapeutic targets in obesity.

show abstract

Section: Introductionmentioning

confidence: 99%

Global epigenetic alterations of mesenchymal stem cells in obesity: the role of vitamin C reprogramming

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The high complexity of the Muc2 protein and the strong secretory capacity of goblet cells make Muc2 susceptible to unfolding/misfolding, leading to ER stress [11]. ER stress is emerging as an important contributor to many chronic diseases, such as obesity and obesity-related metabolic disorders, including dyslipidemia and insulin resistance [12,13]. Indeed, studies in both cellular and mouse models [14], as well as obese individuals [15,16], have demonstrated increased fat mass resulting in chronic ER stress in liver and adipose tissues, leading to the development of insulin resistance and type 2 diabetes [17].…”

Section: Introductionmentioning

confidence: 99%

Docosahexaenoic and Eicosapentaenoic Acids Prevent Altered-Muc2 Secretion Induced by Palmitic Acid by Alleviating Endoplasmic Reticulum Stress in LS174T Goblet Cells

et al. 2019

View full text Add to dashboard Cite

Diets high in saturated fatty acids (FA) represent a risk factor for the development of obesity and associated metabolic disorders, partly through their impact on the epithelial cell barrier integrity. We hypothesized that unsaturated FA could alleviate saturated FA-induced endoplasmic reticulum (ER) stress occurring in intestinal secretory goblet cells, and consequently the reduced synthesis and secretion of mucins that form the protective mucus barrier. To investigate this hypothesis, we treated well-differentiated human colonic LS174T goblet cells with palmitic acid (PAL)—the most commonly used inducer of lipotoxicity in in vitro systems—or n-9, n-6, or n-3 unsaturated fatty acids alone or in co-treatment with PAL, and measured the impact of such treatments on ER stress and Muc2 production. Our results showed that only eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids protect goblet cells against ER stress-mediated altered Muc2 secretion induced by PAL, whereas neither linolenic acid nor n-9 and n-6 FA are able to provide such protection. We conclude that EPA and DHA could represent potential therapeutic nutrients against the detrimental lipotoxicity of saturated fatty acids, associated with type 2 diabetes and obesity or inflammatory bowel disease. These in vitro data remain to be explored in vivo in a context of dietary obesity.

show abstract

“…ER stress results in apoptotic cell death ( 91 ), and ER stress can be attenuated by the protective effect of AMPK activity resulting in reduced apoptosis during DR pathogenesis ( 92 ). Potential mechanistic connections among obesity, insulin resistance, and dyslipidemia resulting in ER stress ( 93 ), provide a strong rationale that such epigenetic phenomena common to dyslipidemia and diabetes can be targeted mechanistically and pharmacologically by activating AMPK.…”

Section: Signaling Pathways and Disease Causing Mechanisms Of Both Dymentioning

confidence: 99%

Emerging Roles of Dyslipidemia and Hyperglycemia in Diabetic Retinopathy: Molecular Mechanisms and Clinical Perspectives

et al. 2021

View full text Add to dashboard Cite

Diabetic retinopathy (DR) is a significant cause of vision loss and a research subject that is constantly being explored for new mechanisms of damage and potential therapeutic options. There are many mechanisms and pathways that provide numerous options for therapeutic interventions to halt disease progression. The purpose of the present literature review is to explore both basic science research and clinical research for proposed mechanisms of damage in diabetic retinopathy to understand the role of triglyceride and cholesterol dysmetabolism in DR progression. This review delineates mechanisms of damage secondary to triglyceride and cholesterol dysmetabolism vs. mechanisms secondary to diabetes to add clarity to the pathogenesis behind each proposed mechanism. We then analyze mechanisms utilized by both triglyceride and cholesterol dysmetabolism and diabetes to elucidate the synergistic, additive, and common mechanisms of damage in diabetic retinopathy. Gathering this research adds clarity to the role dyslipidemia has in DR and an evaluation of the current peer-reviewed basic science and clinical evidence provides a basis to discern new potential therapeutic targets.

show abstract

Endoplasmic reticulum stress epigenetics is related to adiposity, dyslipidemia, and insulin resistance

Cited by 19 publications

References 46 publications

Global epigenetic alterations of mesenchymal stem cells in obesity: the role of vitamin C reprogramming

Global epigenetic alterations of mesenchymal stem cells in obesity: the role of vitamin C reprogramming

Docosahexaenoic and Eicosapentaenoic Acids Prevent Altered-Muc2 Secretion Induced by Palmitic Acid by Alleviating Endoplasmic Reticulum Stress in LS174T Goblet Cells

Emerging Roles of Dyslipidemia and Hyperglycemia in Diabetic Retinopathy: Molecular Mechanisms and Clinical Perspectives

Contact Info

Product

Resources

About