MicroRNA regulation of mitochondrial and ER stress signaling pathways: implications for lipoprotein metabolism in metabolic syndrome

2014 ◽  
Vol 307 (9) ◽  
pp. E729-E737 ◽  
Author(s):  
Patricia Christian ◽  
Qiaozhu Su
Keyword(s):  
Metabolic Syndrome ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Acid Oxidation ◽  
Aberrant Expression ◽  
The Metabolic Syndrome ◽  
Mitochondrial Fatty Acid

The development of metabolic syndrome is closely associated with the deregulation of lipid metabolism. Emerging evidence has demonstrated that microRNAs (miRNAs) are intensively engaged in lipid and lipoprotein metabolism by regulating genes involved in control of intracellular lipid synthesis, mitochondrial fatty acid oxidation, and lipoprotein assembly. Mitochondrial dysfunction induced by altered miRNA expression has been proposed to be a contributing factor in the onset of metabolic diseases, while at the same time, aberrant expression of certain miRNAs is associated with the induction of endoplasmic reticulum (ER) stress induced by nutrient-surplus. These studies position miRNAs as a link between oxidative stress and ER stress, two cellular stress pathways that are deregulated in metabolic disease and are associated with very-low-density lipoprotein (VLDL) overproduction. Dyslipoproteinemia frequently accompanied with metabolic syndrome is initiated largely by the overproduction of VLDL and altered biogenesis of high-density lipoprotein (HDL). In this review, we highlight recent findings on the regulatory impact of miRNAs on the metabolic homeostasis of mitochondria and ER as well as their contribution to the aberrant biogenesis of both VLDL and HDL in the context of metabolic disorders, in an attempt to gain further insights into the molecular mechanisms of dyslipidemia in the metabolic syndrome.

scholarly journals Hyperuricemia is associated with metabolic syndrome in the community very elderly in Chengdu

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Gang Huang ◽  
Junbo Xu ◽  
Tingjie Zhang ◽  
Lin Cai ◽  
Hanxiong Liu ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Logistic Regression ◽  
Metabolic Diseases ◽  
International Diabetes Federation ◽  
Density Lipoprotein ◽  
Cross Sectional Study ◽  
Very Elderly ◽  
Cross Sectional ◽  
The Metabolic Syndrome ◽  
Elderly Chinese

Abstract Hyperuricemia is a risk factor for cardiovascular metabolic diseases. However, in the very elderly, the relationship between hyperuricemia and the metabolic syndrome (MetS) is not yet clear. This study was aimed to investigate the potential association between hyperuricemia and MetS in community very elderly in Chengdu. In this cross-sectional study, 1056 very elderly in the community were enrolled. Serum uric acid (SUA), fast plasma glucose, triglycerides and high–density lipoprotein cholesterol were measured, and then MetS components were calculated. Logistic regression models were used to explore risk factors for MetS in the very elderly. Finally, 1035 participants were included in analysis whose ages ranged between 80 and 100 with a mean age of 83.6 ± 3.4 years. The mean SUA level was 356.2 ± 95.0 µmol/L. The estimated prevalence of MetS in the very elderly was 25.0% vs. 21.6% (international diabetes federation (IDF) criteria vs. Chinese guideline), which was significantly higher for women (IDF criteria:17.3% in men vs 33.6% in women, p < 0.001). Logistic regression has found that participants with hyperuricemia (SUA level > 416 µmol/L in men and > 357 µmol/L in women) had a higher risk (IDF criteria: odds ratio (OR): 2.136, 95% confidence interval(CI): 1.525–2.993, p < 0.001. Chinese guideline: OR: 1.769, 95%CI: 1.249–2.503, p = 0.001) of MetS in very elderly Chinese. MetS is common in the community of very elderly Chinese in Chengdu. Hyperuricemia is associated with MetS in general very elderly and lifestyle changing should also be considered in the very elderly.

scholarly journals Diabetic and Metabolic Programming: Mechanisms Altering the Intrauterine Milieu

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Claudia Eberle ◽  
Christoph Ament
Keyword(s):  
Metabolic Syndrome ◽  
Cardiovascular Diseases ◽  
Maternal Health ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Experimental Studies ◽  
Cardiovascular Changes ◽  
Thrifty Phenotype ◽  
The Metabolic Syndrome ◽  
Thrifty Phenotype Hypothesis

A wealth of epidemiological, clinical, and experimental studies have been linked to poor intrauterine conditions as well as metabolic and associated cardiovascular changes postnatal. These are novel perspectives connecting the altered intrauterine milieu to a rising number of metabolic diseases, such as diabetes, obesity, and hypercholesterolemia as well as the Metabolic Syndrome (Met S). Moreover, metabolic associated atherosclerotic diseases are connected to perigestational maternal health. The “Thrifty Phenotype Hypothesis” introduced cross-generational links between poor conditions during gestation and metabolic as well as cardiovascular alterations postnatal. Still, mechanisms altering the intrauterine milieu causing metabolic and associated atherosclerotic diseases are currently poorly understood. This paper will give novel insights in fundamental concepts connected to specific molecular mechanisms “programming” diabetes and associated metabolic as well as cardiovascular diseases.

scholarly journals Metabolic Syndrome, Obesity, and Gastrointestinal Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Shintaro Fujihara ◽  
Hirohito Mori ◽  
Hideki Kobara ◽  
Noriko Nishiyama ◽  
Mitsuyoshi Kobayashi ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Molecular Mechanisms ◽  
Fasting Glucose ◽  
Density Lipoprotein ◽  
Established Risk Factor ◽  
Metabolic Dysregulation ◽  
The Metabolic Syndrome ◽  
Systemic Factors ◽  
High Fasting Glucose ◽  
Growth Promoting

Metabolic syndrome is a cluster of metabolic abnormalities and is defined as the presence of three or more of the following factors: increased waist circumference, elevated triglycerides, low high-density lipoprotein cholesterol, high blood pressure, and high fasting glucose. Obesity, which is accompanied by metabolic dysregulation often manifested in the metabolic syndrome, is an established risk factor for many cancers. Adipose tissue, particularly visceral fat, is an important metabolic tissue as it secretes systemic factors that alter the immunologic, metabolic, and endocrine milieu and also promotes insulin resistance. Within the growth-promoting, proinflammatory environment of the obese state, cross-talk between macrophages, adipocytes, and epithelial cells occurs via obesity-associated hormones, adipocytokines, and other mediators that may enhance cancer risk and progression. This paper synthesizes the evidence on key molecular mechanisms underlying the obesity-cancer link.

Abstract 215: Fenugreek Seeds Inhibit Hepatic VLDL Overproduction by Attenuating Metabolic Inflammatory Stress

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Jing Shen ◽  
Kaichao Pan ◽  
Dipak Santa ◽  
Qiaozhu Su
Keyword(s):  
Insulin Resistance ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Density Lipoprotein ◽  
Tolerance Test ◽  
Fenugreek Seeds ◽  
Metabolic Inflammation ◽  
Fenugreek Seed ◽  
Mitochondrial Fatty Acid

Fenugreek ( Trigonella foenum-gracecum L ), an annual legume, has been well known for its medicinal properties in treating metabolic diseases. It is a new crop in Nebraska. Its seed contains a number of health-enhancing bioactive compounds, including diosgenin, galactomannan, and 4-hydroxyisoleucine. These compounds synergistically exert multiple health effects on anti-obesity and type 2 diabetes. In this study, we characterized the underlying molecular mechanisms of fenugreek seeds in anti-hyperlipidemia and anti-hyperglycemia. Using a genetic induced hyperlipidemia and a high fat diet (HFD) induced insulin resistance mouse models, we found that a diet rich in fenugreek seeds (2%) was able to lower hypertriglyceridemia induced by depletion of the cyclic AMP responsive element H (CREBH). This phenotype was accompanied by reduced levels of plasma apolipoprotein B100 (apoB) and inflammatory cytokine TNFα. Fenugreek seed feeding inhibited biosynthesis of apoB, and the assembly and secretion of very low density lipoprotein (VLDL) in the liver of CREBH-null mice. Fenugreek seed feeding also induced expression of mitochondrial fatty acid β-oxidation genes, such as PPARα and CPT-1α. Treatment with fenugreek seeds also attenuated ER stress and metabolic inflammation in CREBH-null hepatocytes, indicated by less expression of GRP78 protein, reduced phosphorylation of eIF2α and JNK. Furthermore, fenugreek seed feeding improved insulin sensitivity in a HFD induced insulin resistance mouse model as evidenced by the lower blood glucose levels in a glucose tolerance test and an insulin tolerance test compared to the paired fed-untreated control mice. Fenugreek seeds exerted anti-diabetic effect by enhancing glucose uptake in adipose tissue and liver. Taken together, our study provided new mechanistic insight into the triacylglycerol lowering properties and anti-diabetic nature of fenugreek seeds. This suggests therapeutic potential of fenugreek seed against metabolic disorders and may increase value of Nebraska-grown fenugreek.

scholarly journals Peroxisome Proliferator-Activated Receptor Targets for the Treatment of Metabolic Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Francisco A. Monsalve ◽  
Radha D. Pyarasani ◽  
Fernando Delgado-Lopez ◽  
Rodrigo Moore-Carrasco
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
Glucose Homeostasis ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Atherogenic Dyslipidemia ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
The Metabolic Syndrome

Metabolic syndrome is estimated to affect more than one in five adults, and its prevalence is growing in the adult and pediatric populations. The most widely recognized metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a proinflammatory state as well. Peroxisome proliferator-activated receptors (PPARs) may serve as potential therapeutic targets for treating the metabolic syndrome and its related risk factors. The PPARs are transcriptional factors belonging to the ligand-activated nuclear receptor superfamily. So far, three isoforms of PPARs have been identified, namely, PPAR-α, PPAR-β/δ, and PPAR-γ. Various endogenous and exogenous ligands of PPARs have been identified. PPAR-αand PPAR-γare mainly involved in regulating lipid metabolism, insulin sensitivity, and glucose homeostasis, and their agonists are used in the treatment of hyperlipidemia and T2DM. Whereas PPAR-β/δfunction is to regulate lipid metabolism, glucose homeostasis, anti-inflammation, and fatty acid oxidation and its agonists are used in the treatment of metabolic syndrome and cardiovascular diseases. This review mainly focuses on the biological role of PPARs in gene regulation and metabolic diseases, with particular focus on the therapeutic potential of PPAR modulators in the treatment of thrombosis.

scholarly journals MicroRNAs regulating lipid metabolism in atherogenesis

2012 ◽  
Vol 107 (04) ◽  
pp. 642-647 ◽  
Author(s):  
Katey J. Rayner ◽  
Carlos Fernández-Hernando ◽  
Kathryn J. Moore
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Metabolic Diseases ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Acid Synthesis ◽  
Acid Oxidation ◽  
Element Binding Protein ◽  
Plasma High Density

SummaryMicroRNAs have emerged as important post-transcriptional regulators of lipid metabolism, and represent a new class of targets for therapeutic intervention. Recently, microRNA-33a and b (miR-33a/b) were discovered as key regulators of metabolic programs including cholesterol and fatty acid homeostasis. These intronic microRNAs are embedded in the sterol response element binding protein genes, SREBF2 and SREBF1, which code for transcription factors that coordinate cholesterol and fatty acid synthesis. By repressing a variety of genes involved in cholesterol export and fatty acid oxidation, including ABCA1, CROT, CPT1, HADHB and PRKAA1, miR-33a/b act in concert with their host genes to boost cellular sterol levels. Recent work in animal models has shown that inhibition of these small non-coding RNAs has potent effects on lipoprotein metabolism, including increasing plasma high-density lipo-protein (HDL) and reducing very low density lipoprotein (VLDL) triglyce-rides. Furthermore, other microRNAs are being discovered that also target the ABCA1 pathway, including miR-758, suggesting that miRNAs may work cooperatively to regulate this pathway. These exciting findings support the development of microRNA antagonists as potential therapeutics for the treatment of dyslipidaemia, atherosclerosis and related metabolic diseases.

Lipoprotein transport in the metabolic syndrome: pathophysiological and interventional studies employing stable isotopy and modelling methods

2004 ◽  
Vol 107 (3) ◽  
pp. 233-249 ◽  
Author(s):  
Dick C. CHAN ◽  
P. Hugh R. BARRETT ◽  
Gerald F. WATTS
Keyword(s):  
Metabolic Syndrome ◽  
Stable Isotope ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Mechanisms Of Action ◽  
Biological Data ◽  
Low Density ◽  
The Metabolic Syndrome ◽  
Modelling Methods

The accompanying review in this issue of Clinical Science [Chan, Barrett and Watts (2004) Clin. Sci. 107, 221–232] presented an overview of lipoprotein physiology and the methodologies for stable isotope kinetic studies. The present review focuses on our understanding of the dysregulation and therapeutic regulation of lipoprotein transport in the metabolic syndrome based on the application of stable isotope and modelling methods. Dysregulation of lipoprotein metabolism in metabolic syndrome may be due to a combination of overproduction of VLDL [very-LDL (low-density lipoprotein)]-apo (apolipoprotein) B-100, decreased catabolism of apoB-containing particles and increased catabolism of HDL (high-density lipoprotein)-apoA-I particles. These abnormalities may be consequent on a global metabolic effect of insulin resistance, partly mediated by depressed plasma adiponectin levels, that collectively increases the flux of fatty acids from adipose tissue to the liver, the accumulation of fat in the liver and skeletal muscle, the hepatic secretion of VLDL-triacylglycerols and the remodelling of both LDL (low-density lipoprotein) and HDL particles in the circulation. These lipoprotein defects are also related to perturbations in both lipolytic enzymes and lipid transfer proteins. Our knowledge of the pathophysiology of lipoprotein metabolism in the metabolic syndrome is well complemented by extensive cell biological data. Nutritional modifications may favourably alter lipoprotein transport in the metabolic syndrome by collectively decreasing the hepatic secretion of VLDL-apoB and the catabolism of HDL-apoA-I, as well as by potentially increasing the clearance of LDL-apoB. Several pharmacological treatments, such as statins, fibrates or fish oils, can also correct the dyslipidaemia by diverse kinetic mechanisms of action, including decreased secretion and increased catabolism of apoB, as well as increased secretion and decreased catabolism of apoA-I. The complementary mechanisms of action of lifestyle and drug therapies support the use of combination regimens in treating dyslipoproteinaemia in subjects with the metabolic syndrome.

scholarly journals ER Stress and Lipid Metabolism in Adipocytes

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Beth S. Zha ◽  
Huiping Zhou
Keyword(s):  
Lipid Metabolism ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Metabolic Diseases ◽  
Cell Types ◽  
Β Cells ◽  
The Metabolic Syndrome ◽  
Chronic Activation

The role of endoplasmic reticulum (ER) stress is a rapidly emerging field of interest in the pathogenesis of metabolic diseases. Recent studies have shown that chronic activation of ER stress is closely linked to dysregulation of lipid metabolism in several metabolically important cells including hepatocytes, macrophages, β-cells, and adipocytes. Adipocytes are one of the major cell types involved in the pathogenesis of the metabolic syndrome. Recent advances in dissecting the cellular and molecular mechanisms involved in the regulation of adipogenesis and lipid metabolism indicate that activation of ER stress plays a central role in regulating adipocyte function. In this paper, we discuss the current understanding of the potential role of ER stress in lipid metabolism in adipocytes. In addition, we touch upon the interaction of ER stress and autophagy as well as inflammation. Inhibition of ER stress has the potential of decreasing the pathology in adipose tissue that is seen with energy overbalance.

scholarly journals The Prevalence and Predictors of Hypertension and the Metabolic Syndrome in Police Personnel

2021 ◽  
Vol 18 (13) ◽  
pp. 6728
Author(s):  
James D. Yates ◽  
Jeffrey W. F. Aldous ◽  
Daniel P. Bailey ◽  
Angel M. Chater ◽  
Andrew C. S. Mitchell ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Density Lipoprotein ◽  
Cross Sectional ◽  
Job Type ◽  
The Metabolic Syndrome ◽  
High Prevalence ◽  
Police Personnel ◽  
Behavioural Factors ◽  
Cardiometabolic Risk Markers ◽  
Police Forces

Hypertension and metabolic syndrome (METSYN) are reportedly high in police forces. This may contribute to health deterioration and absenteeism in police personnel. Police forces comprise of staff in ‘operational’ and ‘non-operational’ job types but it is not known if job type is associated to hypertension and METSYN prevalence. This study aimed to explore the prevalence of hypertension and METSYN, the factors associated with the risk of hypertension and METSYN, and compare physiological, psychological, and behavioural factors between operational and non-operational police personnel. Cross-sectional data was collected from 77 operational and 60 non-operational police workers. Hypertension and METSYN were prevalent in 60.5% and 20% of operational and 60.0% and 13.6% of non-operational police personnel, respectively (p > 0.05). Operational job type, moderate organisational stress (compared with low stress) and lower high-density lipoprotein cholesterol were associated with lower odds of hypertension, whereas increasing body mass index was associated with increased odds of hypertension (p < 0.05). None of the independent variables were significantly associated with the odds of METSYN. Operational police had several increased cardiometabolic risk markers compared with non-operational police. Given the high prevalence of hypertension and METSYN in operational and non-operational personnel, occupational health interventions are needed for the police and could be informed by the findings of this study.

Sign in / Sign up

Export Citation Format

Share Document