Chronic dietary n-3 PUFA intervention improves dyslipidaemia and subsequent cardiovascular complications in the JCR:LA-cp rat model of the metabolic syndrome

2011 ◽  
Vol 105 (11) ◽  
pp. 1572-1582 ◽  
Author(s):  
Jing Lu ◽  
Faye Borthwick ◽  
Zahra Hassanali ◽  
Ye Wang ◽  
Rabban Mangat ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Vascular Complications ◽  
Plasma Lipid ◽  
Cardiovascular Complications ◽  
Pufa Supplementation ◽  
The Metabolic Syndrome ◽  
Myocardial Lesions

There is increasing interest in the potential chronic beneficial effects of dietary n-3 PUFA on the metabolic syndrome (MetS) and associated cardiovascular complications. We have recently established that increased dietary n-3 PUFA has a profound acute benefit on fasting lipids and the postprandial pro-inflammatory response in the JCR:LA-cp rat, a model of the MetS. However, it is unclear to what extent chronic dietary n-3 PUFA intervention can modulate the progression of end-stage metabolic and vascular complications. The present study aimed to determine the chronic effects of dietary n-3 PUFA supplementation on fasting and non-fasting dyslipidaemia, insulin resistance and vascular complications in the JCR:LA-cp rodent model. JCR:LA-cp rats were fed an isoenergetic lipid-balanced diet supplemented with 5 % n-3 PUFA (w/w) of the total fat (fish oil-derived EPA/DHA) for 16 weeks. Fasting and non-fasting (postprandial) plasma lipid profile was assessed. Hepatic and adipose tissue was probed for the expression of lipogenic proteins (acyl-CoA carboxylase (ACC), fatty acid synthase (FAS) and sterol regulatory element-binding protein-1 (SREBP-1)), while the activity of Jun N-terminal kinase (JNK) was assessed via Western blot to target phosphorylated JNK protein in primary enterocytes. The frequency of myocardial lesions was assessed by haematoxylin and eosin staining. Increased dietary n-3 PUFA improved both the fasting and postprandial lipid profiles (TAG, cholesterol and apoB48) in the JCR:LA-cp rat, potentially via the down-regulation of the hepatic or adipose tissue expression of lipogenic enzymes (ACC, FAS and SREBP-1). Rats fed the 5 % n-3 PUFA diet had lower (58·2 %; P < 0·01) enterocytic phosphorylated JNK protein and secreted less cholesterol (30 %; P < 0·05) into mesenteric lymph compared with the control. The chronic metabolic benefits of dietary n-3 PUFA may underlie the potential to reduce vascular complications during the MetS, including the observed reduction in the frequency (approximately 80 %) of late-stage 3 myocardial lesions.

Dietary lipids and gene expression

2004 ◽  
Vol 32 (6) ◽  
pp. 999-1002 ◽  
Author(s):  
H.M. Roche
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Transcription Factors ◽  
Fatty Acid ◽  
Regulatory Element ◽  
Nuclear Factor Κb ◽  
Dietary Lipids ◽  
Dietary Fatty Acids ◽  
Dietary Fatty Acid ◽  
The Metabolic Syndrome

Nutrition is a key environmental factor that is particularly involved in the pathogenesis and progression of several polygenic, diet-related diseases. Nutrigenomics refers to the interaction between nutrition and the human genome. Dietary fatty acids interact with multiple nutrient-sensitive transcription factors. This explains the molecular basis of some of the health effects associated with altered dietary fatty acid composition. The metabolic syndrome is a very common condition, characterized by insulin resistance, abdominal obesity, dyslipidaemia and hypertension. It often precedes Type 2 diabetes mellitus, and is associated with a greater risk of cardiovascular disease. Several lines of evidence suggest that the interaction between nutrient-derived metabolic stressors and pro-inflammatory signals play an important role in the aetiology of insulin resistance and the development of the metabolic syndrome. This paper will address the interaction between several nutrient-sensitive transcription factors, including SREBP (sterol-regulatory-element-binding protein) and NFκB (nuclear factor κB), demonstrating how this interaction may be altered with dietary fatty acid interventions.

scholarly journals Suicidal Erythrocyte Death in Metabolic Syndrome

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 154
Author(s):  
Ignazio Restivo ◽  
Alessandro Attanzio ◽  
Luisa Tesoriere ◽  
Mario Allegra
Keyword(s):  
Metabolic Syndrome ◽  
Cell Death ◽  
Endothelial Dysfunction ◽  
Cell Membrane ◽  
Clinical Evidence ◽  
Current Knowledge ◽  
Vascular Complications ◽  
Cardiovascular Complications ◽  
Inflammatory Milieu ◽  
Cardiometabolic Factors

Eryptosis is a coordinated, programmed cell death culminating with the disposal of cells without disruption of the cell membrane and the release of endocellular oxidative and pro-inflammatory milieu. While providing a convenient form of death for erythrocytes, dysregulated eryptosis may result in a series of detrimental and harmful pathological consequences highly related to the endothelial dysfunction (ED). Metabolic syndrome (MetS) is described as a cluster of cardiometabolic factors (hyperglycemia, dyslipidemia, hypertension and obesity) that increases the risk of cardiovascular complications such as those related to diabetes and atherosclerosis. In the light of the crucial role exerted by the eryptotic process in the ED, the focus of the present review is to report and discuss the involvement of eryptosis within MetS, where vascular complications are utterly relevant. Current knowledge on the mechanisms leading to eryptosis in MetS-related conditions (hyperglycemia, dyslipidemia, hypertension and obesity) will be analyzed. Moreover, clinical evidence supporting or proposing a role for eryptosis in the ED, associated to MetS cardiovascular complications, will be discussed.

Abstract 3672: Loss of Perivascular Adipocyte Paracrine Function Leads to Increased Vascular Tone and Glucose Intolerance in Hypertension

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kaivan Khavandi ◽  
Adam Greenstein ◽  
Sarah Withers ◽  
Kazuhiko Sonoyama ◽  
Sarah Lewis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Vascular Tone ◽  
Tnf Alpha ◽  
Perivascular Adipose Tissue ◽  
The Metabolic Syndrome ◽  
Adipocyte Cell ◽  
Therapeutic Opportunity

In order to investigate the contribution of perivascular adipose tissue (PVAT) to arterial function, a total of 55 small arteries harvested from 35 skin biopsies of patients with Metabolic Syndrome and matched controls were mounted as ring preparations in a wire myograph. Contractility to cumulative doses of Norepinephrine in the presence or absence of PVAT showed an anticontractile effect in arteries from healthy volunteers (p=0.009), which was lost in patients with Metabolic Syndrome. Bioassay studies confirmed that PVAT releases a hydrophilic anticontractile factor in health, which is absent in obesity. Using a soluble fragment of the human Type 1 receptor, we identified that the anticontractile factor was adiponectin, which is the sole mediator of vasodilation, acting by increasing endothelial bioavailability of nitric oxide. Significant endothelial dysfunction was observed in patients with Metabolic Syndrome (p<0.001). Quantitative image analysis of adipose tissue revealed significantly increased adipocyte cell size in patients with Metabolic Syndrome, compared with healthy controls (p<0.006). There was immunohistochemical evidence of inflammation with upregulation of TNF-alpha receptor 1 in these patients (p<0.001). Application of exogenous TNF-alpha abolished the anticontractile effect of PVAT by reducing adiponectin bioavailability. Oxidative stress also induced by cytokines TNF-alpha and IL-6 but not IL-1, reduced adiponectin production from PVAT and increased basal tone. When the obese microenvironment was replicated in vitro by inflicting hypoxia on PVAT, adiponectin activity was lost but then rescued by incubation with cytokine antagonists. Further application of the adiponectin receptor fragment abolished PVAT relaxation. We conclude that in healthy arteries, PVAT releases adiponectin which reduces vascular tone. In obesity, this is lost by a cascade of adipocyte hypertrophy, hypoxia, inflammation and oxidative stress. The resulting vasoconstriction contributes to hypertension, hypertriglyceridaemia and insulin resistance. Direct targeting of adiponectin release from PVAT therefore provides a novel therapeutic opportunity in the Metabolic Syndrome.

Increased hepatic lipogenesis but decreased expression of lipogenic gene in adipose tissue in human obesity

2002 ◽  
Vol 282 (1) ◽  
pp. E46-E51 ◽  
Author(s):  
Frédérique Diraison ◽  
Eric Dusserre ◽  
Hubert Vidal ◽  
Monique Sothier ◽  
Michel Beylot
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Energy Restriction ◽  
Mrna Levels ◽  
Hepatic Lipogenesis ◽  
Deuterated Water ◽  
Human Obesity ◽  
Fas Mrna ◽  
Obese Subjects

To determine whether increased lipogenesis contributes to human obesity, we measured (postabsorptive state), in lean and obese subjects, lipid synthesis (deuterated water method) and the mRNA concentration (RT-competitive PCR) in subcutaneous adipose tissue of fatty acid synthase (FAS) and sterol regulatory element-binding protein (SREBP)-1c. Before energy restriction, obese subjects had an increased contribution of hepatic lipogenesis to the circulating triglyceride pool (14.5 ± 1.3 vs. 7.5 ± 1.9%, P < 0.01) without enhancement of cholesterol synthesis. This increased hepatic lipogenesis represented an excess of 2–5 g/day of triglycerides, which would represent 0.7–1.8 kg on a yearly basis. The lipogenic capacity of adipose tissue appeared, on the contrary, decreased with lower FAS mRNA levels ( P < 0.01) and a trend for decreased SREBP-1c mRNA ( P = 0.06). Energy restriction in obese patients decreased plama insulin ( P < 0.05) and leptin ( P < 0.05) and normalized hepatic lipogenesis. FAS mRNA levels were unchanged, whereas SREBP-1c increased. In conclusion, subjects with established obesity have an increased hepatic lipogenesis that could contribute to their excessive fat mass but no evidence for an increased lipogenic capacity of adipose tissue.

Dexamethasone decreases the autotaxin‐lysophosphatidate‐inflammatory axis in adipose tissue: implications for the metabolic syndrome and breast cancer

2018 ◽  
Vol 33 (2) ◽  
pp. 1899-1910 ◽  
Author(s):  
Guanmin Meng ◽  
Xiaoyun Tang ◽  
Zelei Yang ◽  
Yuan Yuan Zhao ◽  
Jonathan M. Curtis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
The Metabolic Syndrome

scholarly journals The metabolic syndrome alters the miRNA signature of porcine adipose tissue-derived mesenchymal stem cells

2017 ◽  
Vol 93 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Yu Meng ◽  
Alfonso Eirin ◽  
Xiang-Yang Zhu ◽  
Hui Tang ◽  
Pritha Chanana ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Mirna Signature ◽  
The Metabolic Syndrome

scholarly journals Micro-RNAS Regulate Metabolic Syndrome-induced Senescence in Porcine Adipose Tissue-derived Mesenchymal Stem Cells through the P16/MAPK Pathway

2018 ◽  
Vol 27 (10) ◽  
pp. 1495-1503 ◽  
Author(s):  
Y. Meng ◽  
A. Eirin ◽  
X.-Y. Zhu ◽  
H. Tang ◽  
L.J. Hickson ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Repair System ◽  
The Metabolic Syndrome ◽  
Micro Rnas ◽  
Mirna Sequencing

Mesenchymal stem cells (MSCs) constitute an important repair system, but may be impaired by exposure to cardiovascular risk factors. Consequently, adipose tissue-derived MSCs from pigs with the metabolic syndrome (MetS) show decreased vitality. A growing number of microRNAs (miRNAs) are recognized as key modulators of senescence, but their role in regulating senescence in MSC in MetS is unclear. We tested the hypothesis that MetS upregulates in MSC expression of miRNAs that can serve as post-transcriptional regulators of senescence-associated (SA) genes. MSCs were collected from swine abdominal adipose tissue after 16 weeks of Lean or Obese diet ( n = 6 each). Next-generation miRNA sequencing (miRNA-seq) was performed to identify miRNAs up-or down-regulated in MetS-MSCs compared with Lean-MSCs. Functional pathways of SA genes targeted by miRNAs were analyzed using gene ontology. MSC senescence was evaluated by p16 and p21 immunoreactivity, H2AX protein expression, and SA-β-Galactosidase activity. In addition, gene expression of p16, p21, MAPK3 (ERK1) and MAPK14, and MSC migration were studied after inhibition of SA-miR-27b. Senescence biomarkers were significantly elevated in MetS-MSCs. We found seven upregulated miRNAs, including miR-27b, and three downregulated miRNAs in MetS-MSCs, which regulate 35 SA genes, particularly MAPK signaling. Inhibition of miR-27b in cultured MSCs downregulated p16 and MARP3 genes, and increased MSC migration. MetS modulates MSC expression of SA-miRNAs that may regulate their senescence, and the p16 pathway seems to play an important role in MetS-induced MSC senescence.

Abstract 1186: Overexpression Of Endothelial Lipase In The Liver Promotes The Clearance Of Plasma Lipids But Accelerates Liver Steatosis In A Mouse Model Of Metabolic Syndrome

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Tomoyuki Yasuda ◽  
Tatsuro Ishida ◽  
Yoko Kojima ◽  
Hanayo Tanaka ◽  
Takeaki Okada ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acid ◽  
Mouse Model ◽  
Fatty Acid Synthase ◽  
Plasma Lipids ◽  
Recombinant Adenovirus ◽  
Mrna Level ◽  
Liver Steatosis ◽  
Endothelial Lipase ◽  
The Metabolic Syndrome

The metabolic syndrome includes high triglyceride (TG) and low HDL-cholesterol (HDL-C) levels in the plasma, and often accompanies steatosis in the liver. Endothelial lipase (EL) is a phospholipase that regulates HDL metabolism. EL is expressed by hepatocytes, while the function of EL in the liver has not been identified. Here, we examined the role of EL in the liver using a mouse model of metabolic syndrome. The EL expression in the liver was analyzed by real-time PCR. It revealed that liver EL expression was significantly increased in obese and diabetic db/db mice compared to that of control mice. To examine the significance of the EL upregulation in the liver, we injected the recombinant adenovirus encoding human EL into mice. The EL overexpression in the liver resulted in a significant decrease in plasma HDL-C, TG, and free fatty acid levels. Interestingly, the EL overexpression in the liver increased liver weight and liver TG content both in wild-type and db/db mice. In db/db mice, particularly, EL overexression accelerated the formation of steatosis by increasing the mRNA level of fatty acid synthase. These findings indicate that EL expression is increased in the liver in the metabolic syndrome. The upregulation of EL promotes the uptake of plasma lipids by hepatocytes, and accelerates the progression of steatosis in db/db mice. Thus EL may play a role in the genesis of steatosis as well as dyslipidemia in the metabolic syndrome.

Sign in / Sign up

Export Citation Format

Share Document