Implications For Metabolic Syndrome Research Articles

Implications of Metabolic Syndrome and Androgen Levels on Erectile Dysfunction in a Sample of Egyptian Subjects: a Case-Controlled Prospective Study

Implications of Metabolic Syndrome and Androgen Levels on Erectile Dysfunction in a Sample of Egyptian Subjects: a Case-Controlled Prospective Study

Vinpocetine Ameliorates Metabolic-Syndrome-Associated Bladder Overactivity in Fructose-Fed Rats by Restoring Succinate-Modulated cAMP Levels and Exerting Anti-Inflammatory Effects in the Bladder Detrusor Muscle

Succinate and its receptor, the G protein-coupled receptor 91 (GPR91), have pathological implications in metabolic syndrome (MetS) and its associated bladder dysfunction, particularly in decreasing bladder cAMP levels and promoting proinflammation. Using fructose-fed rats (FFRs), a rat model of MetS, we investigate the effects of vinpocetine (a phosphodiesterase-1 inhibitor) and celecoxib (a selective cyclooxygenase-2 inhibitor) on MetS-associated bladder overactivity. Phenotypes of the overactive bladder, including increased micturition frequency and a shortened intercontractile interval in cystometry, were observed in FFRs, together with elevated succinate levels in the liver and serum and the downregulation of GPR91 in the liver and urinary bladder. Treatments with vinpocetine and celecoxib improved tissue fibrosis and ameliorated the overexpression of the inflammatory cytokines, such as IL-1β, in the liver and bladder. In bladder organ bath studies, vinpocetine, but not celecoxib, treatment restored the contraction and relaxation responses of the detrusor muscle strip in response to KCl, carbachol, and forskolin stimulation. At a molecular level, vinpocetine and celecoxib treatments modulated the downstream messengers of GPR91 (i.e., ERK1/2 and JNK), suppressed NF-κB and IL-1β expressions in the bladder, and prevented the fibrogenesis observed in FFRs. The exogenous application of succinate to a bladder organ bath significantly reduced the forskolin-induced cAMP production by the detrusor muscle, which was notably restored in the presence of vinpocetine. Together, these results suggest that vinpocetine may alleviate the MetS-associated bladder overactivity by restoring the succinate-modulated detrusor cAMP production and exerting the anti-inflammatory effects in the bladder detrusor muscle.

Mechanistic Insight on the Mode of Action of Colletoic Acid

The natural product colletoic acid (CA) is a selective inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which primarily converts cortisone to the active glucocorticoid (GC) cortisol. Here, CA's mode of action and its potential as a chemical tool to study intracellular GC signaling in adipogenesis are disclosed. 11β-HSD1 biochemical studies of CA indicated that its functional groups at C-1, C-4, and C-9 were important for enzymatic activity; an X-ray crystal structure of 11β-HSD1 bound to CA at 2.6 Å resolution revealed the nature of those interactions, namely, a close-fitting and favorable interactions between the constrained CA spirocycle and the catalytic triad of 11β-HSD1. Structure-activity relationship studies culminated in the development of a superior CA analogue with improved target engagement. Furthermore, we demonstrate that CA selectively inhibits preadipocyte differentiation through 11β-HSD1 inhibition, suppressing other relevant key drivers of adipogenesis (i.e., PPARγ, PGC-1α), presumably by negatively modulating the glucocorticoid signaling pathway. The combined findings provide an in-depth evaluation of the mode of action of CA and its potential as a tool compound to study adipose tissue and its implications in metabolic syndrome.

951b – Dawn to Sunset Fasting for 30 Days Induces Tropomyosin 1, 3 and 4 Genes in Healthy Volunteers: Its Clinical Implications in Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease

951b – Dawn to Sunset Fasting for 30 Days Induces Tropomyosin 1, 3 and 4 Genes in Healthy Volunteers: Its Clinical Implications in Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease

A systematic review of therapeutic uses of fenugreek as hypoglycemic and antihyperlipidemic agent and its implications for metabolic syndrome

A systematic review of therapeutic uses of fenugreek as hypoglycemic and antihyperlipidemic agent and its implications for metabolic syndrome

Anti‐inflammatory bioactives in Alaskan seaweed: implications in metabolic syndrome (1045.14)

A dominant factor underlying the development of metabolic syndrome is abdominal obesity, which is associated with chronic inflammation in adipose tissue. Alaska Native populations, who suffer disproportionately high rates of obesity, have shifted away from traditional dietary foods, like seaweeds, that are a rich source of polyphenols with potential to counteract metabolic syndrome. In this work, Alaskan seaweeds Fucus distichus (FD), Saccharina latissima (SL), Saccharina groenlandica (SG), Alaria marginata (AM), Pyropia fallax (PF), and Ulva lactuca (UL) were evaluated for their potential to ameliorate symptoms of obesity‐linked inflammatory pathways. High levels of phenolics were discovered in ethyl acetate and butanol fractions of AM, FD, and SG (326.8 ‐ 557.2 μg phloroglucinol equivalents (PGE)/mg extract). Fractions of AM, FD, SG, and SL reduced nitric oxide levels in LPS‐induced RAW 264.7 macrophages to basal levels, and assays with 3T3‐L1 adipocytes demonstrated that organic fractions of AM, SL, and UL decreased triglyceride accumulation 13.3 ‐ 24.7%. Subsequent analysis of AM fractions revealed reductions in mRNA expression levels for the inflammatory adipokines IL‐10, MCP‐1, iCAM, and TNF‐α by 92.6%, 50.7%, 67.3%, and 65.4%, respectively. These results support the potential of Alaskan algae to reduce inflammation and obesity in adipose tissue.Grant Funding Source: Supported by the UNC General Administration and NCSU's Plants for Human Health Institute

The Polyphenol Extract from Sechium edule Shoots Inhibits Lipogenesis and Stimulates Lipolysis via Activation of AMPK Signals in HepG2 Cells

Fatty liver may have implications for metabolic syndrome, such as obesity, hypertension, and diabetes. Therefore, the development of pharmacological or natural agents to reduce fat accumulation in the liver is an important effort. The Sechium edule shoots have already been verified to decrease serum lipids and cholesterol and prevent atherosclerosis. However, how Sechium edule shoots modulate hepatic lipid metabolism is unclear. This study was designed to investigate the effects and mechanisms of polyphenol extracts (SPE) of Sechium edule shoots in reducing lipid accumulation in oleic acid-treated HepG2 cells. We found that water extracts (SWE) of Sechium edule shoots could decrease serum and hepatic lipid contents (e.g., triacylglycerol and cholesterol). Furthermore, SWE and SPE through the AMPK (AMP-activating protein kinase) signaling pathway could decrease lipogenic relative enzymes, such as FAS (fatty acid synthase), HMGCoR (HMG-CoA reductase), and SREBPs (sterol regulatory element binding proteins), and increase the expression of CPT-I (carnitine palmitoyltransferase I) and PPARα (peroxisome proliferators activated receptor α), which are critical regulators of hepatic lipid metabolism. These observations suggested that Sechium edule shoots have potential for developing health foods for preventing and remedying fatty liver.

Association between Carbohydrate Intake and Serum Lipids

Background: The effect of dietary carbohydrate on blood lipids has received considerable attention in light of the current trend in lowering carbohydrate intake for weight loss.Objectives: To evaluate the association between carbohydrate intake and serum lipids.Methods: Blood samples and 24-hour dietary and physical activity recall interviews were obtained from each subject at quarterly intervals for five consecutive quarters between 1994 and 1998 from 574 healthy adults in Central Massachusetts. Relationships between serum lipids and dietary carbohydrate factors were assessed using linear mixed models and adjusting for other risk factors known to be related to blood lipids. Both cross-sectional and longitudinal results were reported.Results: Cross-sectional analysis results from this study suggest that higher total carbohydrate intake, percentage of calories from carbohydrate, glycemic index (GI) and/or glycemic load (GL) are related to lower high-density lipoprotein cholesterol (HDL-C) and higher serum triacylglycerol levels, while higher total carbohydrate intake and/or GL are related to lower total and low-density lipoprotein cholesterol (LDL-C) levels. In a one-year longitudinal analysis, GL was positively associated with total and LDL-C levels, and there was an inverse association between percentage of calories from carbohydrate and HDL-C levels.Conclusions: Results suggest that there is a complex and predominantly unfavorable effect of increased intake of highly processed carbohydrate on lipid profile, which may have implications for metabolic syndrome, diabetes, and coronary heart disease. Further studies in the form of randomized controlled trials are required to investigate these associations and determine the implications for lipid management.

Soluble guanylate cyclase (sGC) down-regulation by abnormal extracellular matrix proteins as a novel mechanism in vascular dysfunction: Implications in metabolic syndrome☆

Vascular dysfunction plays a role in most if not all cardiovascular disorders. Vascular dysfunction is defined as impaired vasodilation in response to agonists such as acetylcholine (ACh) that mediate vascular smooth muscle relaxation through release of the endothelial derived relaxing factor (EDRF) nitric oxide (NO). There is a wealth of literature to support the understanding that endothelial dysfunction is due to a decreased NO synthesis or an increased NO inactivation. Endothelial dysfunction is generally thought to be responsible for vascular dysfunction, and the terms are often used interchangeably. But the mechanism(s) responsible for vascular dysfunction is (are) far from being completely understood, and labeling all vascular dysfunction as endothelial dysfunction may be application of a misnomer in some cases. Alterations in the cell signaling cascade downstream of NO production and release could explain vascular dysfunction in certain conditions. Nowadays, it is textbook information that NO induces cell relaxation by interacting with sGC and causing an increase in cyclic guanosine monophosphate (cGMP). The end result is thought to be a decrease in intracellular cytoplasmic calcium due to decreased intracellular calcium release [1] and/or increased cGMP-dependent calcium pump activity [1] and/or due to decreased calcium influx because of the opening of K+ channels, resulting in hyperpolarization and the consequent closing of L-type Ca … *Tel.: +1 317 274 9765; fax: +1 317 274 3318. Email address: spacker1{at}iupui.edu