Browsing by Subject "metabolic syndrome"
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Item Associations of plasma very-long-chain SFA and the metabolic syndrome in adults(Cambridge, 2018-10) Zhao, Jing; Li, Xiaofan; Li, Xiang; Chu, Qianqian; Zhou, Yunhua; Li, Zi; Zhang, Hong; Brenna, Thomas J.; Song, Yiqing; Gao, Ying; Epidemiology, School of Public HealthPlasma levels of very-long-chain SFA (VLCSFA) are associated with the metabolic syndrome (MetS). However, the associations may vary by different biological activities of individual VLCSFA or population characteristics. We aimed to examine the associations of VLCSFA and MetS risk in Chinese adults. Totally, 2008 Chinese population aged 35–59 years were recruited and followed up from 2010 to 2012. Baseline MetS status and plasma fatty acids data were available for 1729 individuals without serious diseases. Among 899 initially metabolically healthy individuals, we identified 212 incident MetS during the follow-up. Logistic regression analysis was used to estimate OR and 95 % CI. Cross-sectionally, each VLCSFA was inversely associated with MetS risk; comparing with the lowest quartile, the multivariate-adjusted OR for the highest quartile were 0·18 (95 % CI 0·13, 0·25) for C20 : 0, 0·26 (95 % CI 0·18, 0·35) for C22 : 0, 0·19 (95 % CI 0·13, 0·26) for C24 : 0 and 0·16 (0·11, 0·22) for total VLCSFA (all Pfor trend<0·001). The associations remained significant after further adjusting for C16 : 0, C18 : 0, C18 : 3n-3, C22 : 6n-3, n-6 PUFA and MUFA, respectively. Based on follow-up data, C20 : 0 or C22 : 0 was also inversely associated with incident MetS risk. Among the five individual MetS components, higher levels of VLCSFA were most strongly inversely associated with elevated TAG (≥1·7 mmol/l). Plasma levels of VLCSFA were significantly and inversely associated with MetS risk and individual MetS components, especially TAG. Further studies are warranted to confirm the findings and explore underlying mechanisms.Item Circadian clock control of hepatic lipid metabolism: role of small heterodimer partner (Shp)(BMJ Journals, 2016-10) Wang, Li; Liangpunsakul, Suthat; Medicine, School of MedicineHepatic steatosis, the accumulation of triglyceride droplets in the hepatocytes, is a common hepatic pathology seen in subjects with obesity/metabolic syndrome and those with excessive alcohol use. The pathogenesis underlying hepatic steatosis is complex. Recent studies have shown the specific role played by the molecular clock mechanism in the control of lipid metabolism and that the disruption of these tissue clocks may lead to the disturbances in lipid homeostasis. This review reports a novel role of small heterodimer partner in maintaining triglyceride and lipoprotein homeostasis through neuronal PAS domain protein 2.Item Contribution of K+ Channels to Coronary Dysfunction in Metabolic Syndrome(2009-06-24T12:58:39Z) Watanabe, Reina; Tune, Johnathan D.Coronary microvascular function is markedly impaired by the onset of the metabolic syndrome and may be an important contributor to the increased cardiovascular events associated with this mutlifactorial disorder. Despite increasing appreciation for the role of coronary K+ channels in regulation of coronary microvascular function, the contribution of K+ channels to the deleterious influence of metabolic syndrome has not been determined. Accordingly, the overall goal of this investigation was to delineate the mechanistic contribution of K+ channels to coronary microvascular dysfunction in metabolic syndrome. Experiments were performed on Ossabaw miniature swine fed a normal maintenance diet or an excess calorie atherogenic diet that induces the classical clinical features of metabolic syndrome including obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, hyperleptinemia, and atherosclerosis. Experiments involved in vivo studies of coronary blood flow in open-chest anesthetized swine as well as conscious, chronically instrumented swine and in vitro studies in isolated coronary arteries, arterioles, and vascular smooth muscle cells. We found that coronary microvascular dysfunction in the metabolic syndrome significantly impairs coronary vasodilation in response to metabolic as well as ischemic stimuli. This impairment was directly related to decreased membrane trafficking and functional expression of BKCa channels in vascular smooth muscle cells that was accompanied by augmented L-type Ca2+ channel activity and increased intracellular Ca2+ concentration. In addition, we discovered that impairment of coronary vasodilation in the metabolic syndrome is mediated by reductions in the functional contribution of voltage-dependent K+ channels to the dilator response. Taken together, findings from this investigation demonstrate that the metabolic syndrome markedly attenuates coronary microvascular function via the diminished contribution of K+ channels to the overall control of coronary blood flow. Our data implicate impaired functional expression of coronary K+ channels as a critical mechanism underlying the increased incidence of cardiac arrhythmias, infarction and sudden cardiac death in obese patients with the metabolic syndrome.Item Coronary artery disease progression and calcification in metabolic syndrome(2014) McKenney, Mikaela Lee; Sturek, Michael Stephen; Evans-Molina, Carmella; Moe, Sharon M.; Tune, Johnathan D.For years, the leading killer of Americans has been coronary artery disease (CAD), which has a strong correlation to the U.S. obesity epidemic. Obesity, along with the presence of other risk factors including hyperglycemia, hypercholesterolemia, dyslipidemia, and high blood pressure, comprise of the diagnosis of metabolic syndrome (MetS). The presentation of multiple MetS risk factors increases a patients risk for adverse cardiovascular events. CAD is a complex progressive disease. We utilized the superb model of CAD and MetS, the Ossabaw miniature swine, to investigate underlying mechanisms of CAD progression. We studied the influence of coronary epicardial adipose tissue (cEAT) and coronary smooth muscle cell (CSM) intracellular Ca2+ regulation on CAD progression. By surgical excision of cEAT from MetS Ossabaw, we observed an attenuation of CAD progression. This finding provides evidence for a link between local cEAT and CAD progression. Intracellular Ca2+ is a tightly regulated messenger in CSM that initiates contraction, translation, proliferation and migration. When regulation is lost, CSM dedifferentiate from their mature, contractile phenotype found in the healthy vascular wall to a synthetic, proliferative phenotype. Synthetic CSM are found in intimal plaque of CAD patients. We investigated the changes in intracellular Ca2+ signaling in enzymatically isolated CSM from Ossabaw swine with varying stages of CAD using the fluorescent Ca2+ indicator, fura-2. This time course study revealed heightened Ca2+ signaling in early CAD followed by a significant drop off in late stage calcified plaque. Coronary artery calcification (CAC) is a result of dedifferentiation into an osteogenic CSM that secretes hydroxyapatite in the extracellular matrix. CAC is clinically detected by computed tomography (CT). Microcalcifications have been linked to plaque instability/rupture and cannot be detected by CT. We used 18F-NaF positron emission tomography (PET) to detect CAC in Ossabaw swine with early stage CAD shown by mild neointimal thickening. This study validated 18F-NaF PET as a diagnostic tool for early, molecular CAC at a stage prior to lesions detectable by CT. This is the first report showing non-invasive PET resolution of CAC and CSMC Ca2+ dysfunction at an early stage previously only characterized by invasive cellular Ca2+ imaging.Item Intracellular Ca2+ Dysregulation in Coronary Smooth Muscle Is Similar in Coronary Disease of Humans and Ossabaw Miniature Swine(Springer, 2022-02) Badin, Jill K.; Eggenberger, Caleb; Rodenbeck, Stacey Dineen; Hashmi, Zubair A.; Wang, I-wen; Garcia, Jose P.; Alloosh, Mouhamad; Sturek, Michael; Anatomy and Cell Biology, School of MedicineIntracellular free Ca2+ ([Ca2+]i) dysregulation occurs in coronary smooth muscle (CSM) in atherosclerotic coronary artery disease (CAD) of metabolic syndrome (MetS) swine. Our goal was to determine how CAD severity, arterial structure, and MetS risk factors associate with [Ca2+]i dysregulation in human CAD compared to changes in Ossabaw miniature swine. CSM cells were dispersed from coronary arteries of explanted hearts from transplant recipients and from lean and MetS swine with CAD. CSM [Ca2+]i elicited by Ca2+ influx and sarcoplasmic reticulum (SR) Ca2+ release and sequestration was measured with fura-2. Increased [Ca2+]i signaling was associated with advanced age and a greater media area in human CAD. Decreased [Ca2+]i signaling was associated with a greater number of risk factors and a higher plaque burden in human and swine CAD. Similar [Ca2+]i dysregulation exhibited in human and Ossabaw swine CSM provides strong evidence for the translational relevance of this large animal model.