scholarly journals DHA Supplementation Attenuates MI-Induced LV Matrix Remodeling and Dysfunction in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
I. Habicht ◽  
G. Mohsen ◽  
L. Eichhorn ◽  
S. Frede ◽  
C. Weisheit ◽  
...  
Keyword(s):  
Docosahexaenoic Acid ◽  
Mrna Expression ◽  
Myosin Heavy Chain Isoforms ◽  
Lv Function ◽  
Peroxisome Proliferator ◽  
Matrix Remodeling ◽  
Collagen Deposition ◽  
Macrophage Phenotype ◽  
Omega 3 ◽  
Myocardial Ischemia And Reperfusion

Objective. Myocardial ischemia and reperfusion (I/R) injury is associated with oxidative stress and inflammation, leading to scar development and malfunction. The marine omega-3 fatty acids (ω-3 FA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are mediating cardioprotection and improving clinical outcomes in patients with heart disease. Therefore, we tested the hypothesis that docosahexaenoic acid (DHA) supplementation prior to LAD occlusion-induced myocardial injury (MI) confers cardioprotection in mice. Methods. C57BL/6N mice were placed on DHA or control diets (CD) beginning 7 d prior to 60 min LAD occlusion-induced MI or sham surgery. The expression of inflammatory mediators was measured via RT-qPCR. Besides FACS analysis for macrophage quantification and subtype evaluation, macrophage accumulation as well as collagen deposition was quantified in histological sections. Cardiac function was assessed using a pressure-volume catheter for up to 14 d. Results. DHA supplementation significantly attenuated the induction of peroxisome proliferator-activated receptor-α (PPAR-α) (2.3±0.4 CD vs. 1.4±0.3 DHA) after LAD occlusion. Furthermore, TNF-α (4.0±0.6 CD vs. 1.5±0.2 DHA), IL-1β (60.7±7.0 CD vs. 11.6±1.9 DHA), and IL-10 (223.8±62.1 CD vs. 135.5±38.5 DHA) mRNA expression increase was diminished in DHA-supplemented mice after 72 h reperfusion. These changes were accompanied by a less prominent switch in α/β myosin heavy chain isoforms. Chemokine mRNA expression was stronger initiated (CCL2 6 h: 32.8±11.5 CD vs. 78.8±13.6 DHA) but terminated earlier (CCL2 72 h: 39.5±7.8 CD vs. 8.2±1.9 DHA; CCL3 72 h: 794.3±270.9 CD vs. 258.2±57.8 DHA) in DHA supplementation compared to CD mice after LAD occlusion. Correspondingly, DHA supplementation was associated with a stronger increase of predominantly alternatively activated Ly6C-positive macrophage phenotype, being associated with less collagen deposition and better LV function (EF 14 d: 17.6±2.6 CD vs. 31.4±1.5 DHA). Conclusion. Our data indicate that DHA supplementation mediates cardioprotection from MI via modulation of the inflammatory response with timely and attenuated remodeling. DHA seems to attenuate MI-induced cardiomyocyte injury partly by transient PPAR-α downregulation, diminishing the need for antioxidant mechanisms including mitochondrial function, or α- to β-MHC isoform switch.

scholarly journals Opposing Effects of Omega-3 and Omega-6 Long Chain Polyunsaturated Fatty Acids on the Expression of Lipogenic Genes in Omental and Retroperitoneal Adipose Depots in the Rat

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
B. S. Muhlhausler ◽  
R. Cook-Johnson ◽  
M. James ◽  
D. Miljkovic ◽  
E. Duthoit ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Fatty Acid Synthase ◽  
Peroxisome Proliferator ◽  
Omega 3 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Total N ◽  
Altered Expression ◽  
Lipogenic Genes ◽  
Omega 6 ◽  
Glycerol 3 Phosphate Dehydrogenase

This study aimed to determine the effect of varying dietary intake of the major n-3 PUFA in human diets,α-linolenic acid (ALA; 18 : 3n-3), on expression of lipogenic genes in adipose tissue. Rats were fed diets containing from 0.095%en to 6.3%en ALA and a constant n-6 PUFA level for 3 weeks. Samples from distinct adipose depots (omental and retroperitoneal) were collected and mRNA expression of the pro-lipogenic transcription factors Sterol-Retinoid-Element-Binding-Protein1c (SREBP1c) and Peroxisome Proliferator Activated Receptor-γ(PPARγ), lipogenic enzymes Sterol-coenzyme Desaturase1 (SCD-1), Fatty Acid Synthase (FAS), lipoprotein lipase (LPL) and glycerol-3-phosphate dehydrogenase (G3PDH) and adipokines leptin and adiponectin determined by qRT-PCR. Increasing dietary ALA content resulted in altered expression of SREBP1c, FAS and G3PDH mRNA in both adipose depots. SREBP1c mRNA expression was related directly to n-6 PUFA concentrations (omental,r2=.71;P<.001; Retroperitoneal,r2=.20;P<.002), and inversely to n-3 PUFA concentrations (omental,r2=.59;P<.001; Retroperitoneal,r2=.19;P<.005) independent of diet. The relationship between total n-6 PUFA and SREBP1c mRNA expression persisted when the effects of n-3 PUFA were controlled for. Altering red blood cell concentrations of n-3 PUFA is thus associated with altered expression of lipogenic genes in a depot-specific manner and this effect is modulated by prevailing n-6 PUFA concentrations.

Cognitive and mood effects of 8 weeks' supplementation with 400 mg or 1000 mg of the omega-3 essential fatty acid docosahexaenoic acid (DHA) in healthy children aged 10–12 years

2009 ◽  
Vol 12 (2) ◽  
pp. 48-56 ◽  
Author(s):  
David O. Kennedy ◽  
Philippa A. Jackson ◽  
Jade M. Elliott ◽  
Andrew B. Scholey ◽  
Bernadette C. Robertson ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Docosahexaenoic Acid ◽  
Essential Fatty Acid ◽  
Healthy Children ◽  
Omega 3 ◽  
Mood Effects

scholarly journals Reverse Feeding Suppresses the Activity of the GH Axis in Rats and Induces a Preobesogenic State

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 869-882 ◽  
Author(s):  
Camilla A.-M. Glad ◽  
Edward E. J. Kitchen ◽  
Gemma C. Russ ◽  
Sophie M. Harris ◽  
Jeffrey S. Davies ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Phase Inversion ◽  
Fatty Acid Synthase ◽  
Uncoupling Protein ◽  
Expression Patterns ◽  
Pulse Height ◽  
Male Rats ◽  
Dark Phase ◽  
Peroxisome Proliferator ◽  
Gh Secretion

Reversed feeding (RF) is known to disrupt hormone rhythmicity and metabolism. Although these effects may be mediated in part by phase inversion of glucocorticoid secretion, the precise mechanism is incompletely characterized. In this study, we demonstrate that acute nocturnal food deprivation in male rats suppressed the amplitude of spontaneous GH secretion during the dark phase by 62% (P &lt; 0.001), without affecting baseline secretion. Prolonged RF, which reduced pituitary weight (by 22%; P &lt; 0.05), also suppressed GH pulse height sufficiently to reduce skeletal growth (by 4–5%; P &lt; 0.01) and terminal liver weight (by 11%; P &lt; 0.001). Despite this suppression of the GH axis, proportionate adiposity was not elevated, probably due to the accompanying 16% reduction in cumulative food intake (P &lt; 0.01). We demonstrate that RF also resulted in phase inversion of core clock gene expression in liver, abdominal white adipose tissue (WAT) and skeletal muscle, without affecting their expression patterns in the suprachiasmatic nucleus. In addition, RF resulted in phase inversion of hepatic peroxisome proliferator-activated receptor γ2 mRNA expression, a 3- to 5-fold elevation in fatty acid synthase mRNA in WAT in both light- and dark-phase samples (P &lt; 0.01) and an elevation in muscle uncoupling protein 3 mRNA expression at the beginning of the light phase (P &lt; 0.01). Consumption of a high-fat diet increased inguinal (by 36%; P &lt; 0.05) and retroperitoneal WAT weight (by 72%; P &lt; 0.01) only in RF-maintained rats, doubling the efficiency of lipid accumulation (P &lt; 0.05). Thus, RF not only desynchronizes central and peripheral circadian clocks, and suppresses nocturnal GH secretion, but induces a preobesogenic state.

Docosahexaenoic Acid, a Peroxisome Proliferator-Activated Receptor-α Activator, Induces Apoptosis in Vascular Smooth Muscle Cells by Activation of P38 Mitogen-Activated Protein Kinase

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 679-679
Author(s):  
Quy N Diep ◽  
Rhian M Touyz ◽  
Ernesto L Schiffrin
Keyword(s):  
Smooth Muscle ◽  
Cytochrome C ◽  
Docosahexaenoic Acid ◽  
Vascular Smooth Muscle ◽  
Morphological Changes ◽  
Mitogen Activated Protein Kinase ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Mitogen Activated Protein ◽  
P38 Mapks

9 Omega-3 fatty acids (n-3 FAs) exert a blood pressure-lowering effect in hypertension, possibly by influencing vascular structure. We previously demonstrated that n-3 FAs might induce vascular smooth muscle cell (VSMC) apoptosis, which could exert an effect on structure of blood vessels. This study investigated signaling pathways through which n-3 FAs mediate apoptosis in VSMCs. Cultured Mesenteric VSMCs from Sprague Dawley rats were stimulated with docosahexaenoic acid (DHA), a representative n-3 FA. Morphological changes of apoptosis and DNA fragmentation were examined by phase-contrast microscopy and fluorescence microscopy with Hoechst 33342 staining. To clarify possible pathways of apoptosis, expression of phosphorylated p38 mitogen-activated protein kinases (p38 MAPKs), bax, bcl-2, cytochrome C and peroxisome proliferator-activated receptors-α (PPARs-α) was evaluated by Western blot analysis. DHA treatment induced cell shrinkage, cell membrane blebbing and apoptotic bodies in VSMCs. DHA increased apoptosis (%) in a time-dependent manner to 1.5±0.1, 3.6±0.5, 7.1±0.4, 22.5±0.6, 50.8±1.8 and 61.4±0.9 after 0, 1, 3, 6, 17, and 24 h, respectively. DHA time-dependently activated p38 MAPKs, bax, PPARs-α and cytochrome C with maximal effects obtained after 5, 30 min, 1 h and 3 h, respectively to 551±42, 245±55, 310±12 and 407±14.7 % of controls, respectively. SB-203580 (10 -5 M) and SB-202190 (10 -5 M), selective p38 inhibitors, reduced DHA-elicited apoptosis and expression of PPARs-α, but had no effect on expression of bax or cytochrome C. The present results indicate that DHA induces apoptosis in VSMCs through at least two distinct mechanisms: (i) a p38-dependent pathway that regulates PPAR-α and (ii) a p38-independent pathway via dissipation of mitochondrial transmembrane potential. The death-signaling pathway mediated by DHA may involve an integration of these multiple pathways. By triggering VSMC apoptosis, DHA could play a pathophysiological role in vascular remodeling in cardiovascular disease.

scholarly journals Rapid response to leptin therapy in a FPLD patient with a novel PPARG missense variant

2021 ◽  
Vol 2021 ◽  
Author(s):  
Fiona Melzer ◽  
Corinna Geisler ◽  
Dominik M Schulte ◽  
Matthias Laudes
Keyword(s):  
Missense Variant ◽  
Metabolic Phenotype ◽  
Lipid Lowering ◽  
Peroxisome Proliferator ◽  
Lipid Lowering Therapy ◽  
List Type ◽  
Omega 3 ◽  
Skin Reactions ◽  
Acid Therapy ◽  
Partial Lipodystrophy

Summary Familial partial lipodystrophy (FPLD) syndromes are rare heterogeneous disorders especially in women characterized by selective loss of adipose tissue, reduced leptin levels and severe metabolic abnormalities. Here we report a 34-year-old female with a novel heterozygotic c.485 thymine>guanine (T>G) missense variant (p.phenylalanine162cysteine; (Phe162Cys)) in exon 4 of the peroxisome proliferator-activated receptor gamma (PPARG) gene, developing a non-ketotic diabetes and severe hypertriglyceridemia with triglyceride concentrations >50 mmol/L. In this case, a particular interesting feature in comparison to other known PPARG mutations in FPLD is that while glycaemic control could be achieved through standard anti-diabetic medication, hypertriglyceridemia did neither respond to fibrate nor to omega-3-fatty acid therapy. This might suggest a lipid metabolism driven phenotype of the novel PPARG c.485T>G missense variant. Notably, recombinant leptin replacement therapy (metreleptin (Myalepta®)) was initiated showing a rapid and profound effect on triglyceride levels as well as on liver function tests and satiety feeling. Unfortunately, severe allergic skin reactions developed at the side of injection which could be covered by anti-histaminc treatment. We conclude that the heterozygous PPARG c.485T>G variant is a yet undescribed molecular basis underlying FPLD with difficulties predominantly to control hypertriglyceridemia and that recombinant leptin therapy may be effective in affected subjects. Learning points Heterozygous c.485T>G variant in PPARG is most likely a cause for FPLD in humans. This variant results in a special metabolic phenotype with a predominant dysregulation of triglyceride metabolism not responding to standard lipid lowering therapy. Recombinant leptin therapy is effective in rapidly improving hypertriglyceridemia.

scholarly journals The Alterations of Endometrial and Myometrial Receptivity in Early Pregnant Gilts in Response to Estrus Induction With PMSG/hCG

2021 ◽  
Author(s):  
Magdalena Szymanska ◽  
Agnieszka Blitek
Keyword(s):  
Mrna Expression ◽  
Standard Procedure ◽  
Oxytocin Receptor ◽  
Hormonal Control ◽  
Receptor Expression ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Uterine Receptivity ◽  
Swine Industry ◽  
Junction Protein

Abstract Background: The hormonal control of ovulation has become a standard procedure in the swine industry. However, exogenous gonadotropins can be detrimental to reproductive function, affecting follicle development, corpus luteum formation, and embryo development and survival. Much less is known about uterine receptivity in gilts with induced estrus. Therefore, our objective was to determine the effect of estrus induction with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) on the expression of steroid, prostaglandin, cytokine, and oxytocin receptors, as well as nuclear factor kappa B subunit 1 (NFKB1), peroxisome proliferator activated receptor gamma (PPARG), and gap junction protein alpha 1 (GJA1), in the endometrium and myometrium of early pregnant gilts. Twenty prepubertal gilts received 750 IU PMSG and 500 IU hCG 72 h later, while eighteen prepubertal gilts in the control group were observed daily for estrus behavior. All gilts were inseminated in their first estrus and slaughtered on days 10, 12, and 15 of pregnancy to collect uterine tissues for mRNA expression analyses using real-time PCR.Results: Estrus induction did not affect progesterone receptor expression in either uterine tissue. In the endometrium, greater mRNA expression of estrogen receptors (ESR1 and ESR2), androgen receptor (AR), prostaglandin (PG) E2 receptors (PTGER2 and PTGER4), PGF2α receptor (PTGFR), interleukin 6 receptor (IL6R), tumor necrosis factor α receptors (TNFRSF1A and TNFRSF1B), and oxytocin receptor (OXTR) was detected in the control than in the PMSG/hCG-treated gilts (P < 0.05). In the myometrium, concentrations of AR, PTGER2, PTGFR, and NFKB1 transcripts were lower, while PGI2 receptor and PPARG transcripts were elevated in gilts with gonadotropin-induced estrus as compared with naturally ovulated gilts (P < 0.05). Furthermore, the administration of PMSG/hCG resulted in the greater expression of GJA1 mRNA in both the endometrium and myometrium of day 15 pregnant gilts (P < 0.05). Conclusions: Estrus induction with PMSG/hCG in prepubertal gilts may affect steroid, prostaglandin, cytokine, and oxytocin receptor expression in the endometrium and myometrium, thereby altering uterine receptivity to local or systemic factors. This may, in turn, contribute to disorders in embryo-maternal interactions and the process of implantation.

scholarly journals Omega-3 fatty acids and cardiovascular disease: epidemiology and effects on cardiometabolic risk factors

2014 ◽  
Vol 5 (9) ◽  
pp. 2004-2019 ◽  
Author(s):  
Trevor A. Mori
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Fatty Acids ◽  
Docosahexaenoic Acid ◽  
Cardiometabolic Risk ◽  
Epidemiological Studies ◽  
Fish Oils ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Disease Epidemiology

Clinical and epidemiological studies provide support that the polyunsaturated omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid from fish and fish oils are cardioprotective, particularly in the setting of secondary prevention.

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