Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of antiretroviral combination therapy in HIV has been associated with lipodystrophy and several metabolic risk factors. We postulated that patients with HIV-lipodystrophy have impaired adipose tissue free fatty acid (FFA) trapping and, consequently, increased hepatic FFA delivery. We investigated FFA, hydroxybutyric acid (HBA; reflecting hepatic FFA oxidation), and triglyceride (TG) changes after a high fat meal in HIV-infected males with (LIPO; n = 26) and without (NONLIPO; n = 12) lipodystrophy and in healthy males (n = 35). Because defective peripheral FFA trapping has been associated with impaired action of complement component 3 (C3), we also determined postprandial C3 concentrations. The LIPO group had higher homeostasis model assessment scores compared with the other groups. Areas under the curve (AUCs) for FFA, HBA, and TG were higher in the LIPO group than in the NONLIPO group or the controls. No differences in TG-AUC, FFA-AUC, and HBA-AUC were observed between the NONLIPO group and controls. In HIV-infected patients, FFA-AUC and HBA-AUC were inversely related to sc adipose tissue area. Plasma C3 showed a postprandial increase in healthy controls, but not in the HIV-infected groups. C3 was not related to body fat distribution, postprandial FFA, or HBA. The present data suggest disturbed postprandial FFA metabolism in patients with HIV-lipodystrophy, most likely due to inadequate incorporation of FFA into TG in sc adipose tissue, but do not support a major role for C3 in these patients. The higher postprandial HBA levels reflect increased hepatic FFA delivery and may aggravate insulin resistance and dyslipidemia, leading to increased cardiovascular risk.
 ...
PMID:In vivo evidence of impaired peripheral fatty acid trapping in patients with human immunodeficiency virus-associated lipodystrophy. 1578 7

Hyperlipidemia has been well recognized as a striking feature of nephrotic syndrome and other renal diseases. However, the underlying pathophysiological mechanisms still have not yet been elucidated. In this study, we evaluated acylation-stimulating protein (ASP) and complement component 3 (C3) in children (n=48) with various forms of proteinuric renal disease [nephrotic syndrome, acute poststreptococcal infection glomerulonephritis (APSGN), and lupus nephritis (LN)] in comparison with age- and gender-matched controls (n=279). In children with proteinuric renal disease, various aberrations in plasma lipids were noted, including increased triglyceride, cholesterol, and low-density lipoprotein cholesterol (LDL-C) (all p<0.0001). Whereas C3 was not altered in children with nephrotic syndrome (1.05+/-0.05 g/L vs. 1.29+/-0.04 controls), the decrease was pronounced in children with LN and APSGN (0.42+/-0.11, p<0.05 and 0.30+/-0.06, p<0.001, respectively). Plasma C3 correlated positively with lipid parameters [triglyceride, cholesterol, LDL-C, apolipoprotein B (apoB), high-density lipoprotein cholesterol (HDL-C) and apoA1] and inversely with total protein, blood urea nitrogen, and creatinine. By contrast, plasma ASP was significantly elevated in all proteinuric renal diseases (101.4+/-7.1 nmol/L nephrotic syndrome, 90.9+/-14.1 LN, and 81.8+/-7.2 APSGN vs. 44.3+/-1.5 controls, p<0.05 to p<0.001), and this increase was correlated with changes in lipid parameters (triglycerides and apoA1). In summary, these results demonstrate alterations in C3 and ASP that may contribute to or compensate for dyslipidemia.
 ...
PMID:Increased plasma acylation-stimulating protein in pediatric proteinuric renal disease. 1825 59

This review summarizes available evidence on the role of serum complement component 3 (C3), produced by liver, adipocytes and activated macrophages at inflammation sites, and C3 cleavage products linking lipoproteins and metabolism to immunity. C3 and cleavage products are modified in several associated metabolic disorders including obesity, insulin resistance, type-2 diabetes, dyslipidemia, and cardiovascular diseases. Circulating C3 is independently and linearly associated with serum triglycerides, C-reactive protein (CRP), waist circumference and in some populations inversely with current smoking. The complement cascade is activated during myocardial ischemia and likely mediates immune and inflammatory responses in ischemic myocardium. Serum complement activation is elevated in unstable rather than stable angina pectoris suggesting added contribution to damage extension in acute coronary syndromes. In logistic regression models for incident metabolic syndrome (MetS), increasing C3 concentrations predicted MetS in women, after adjusting for continuous values of 3 major MetS components and other confounders, with a relative risk similar in magnitude to an established component suggesting elevated C3 likely constitutes part of the cluster of MetS in women. C3 interacts with MetS in men for independently conferring risk of incident type-2 diabetes and coronary heart disease (CHD). In women, though C3 is equally predictive of cardiometabolic risk, it is less so additively to MetS components or to CRP. Evidence suggests that circulating C3 might serve as a signal for an immune process that enhances - via mediation of increased apolipoprotein (apo) E levels - the development of dysfunctional apoA-I particles rendering them diabetogenic and atherogenic in populations prone to MetS or subsets of populations harboring impaired glucose tolerance. C3 activation also leads to production of chemoattractants C3a and C5a, and acylation stimulating protein (ASP, C3adesArg), a lipogenic hormone, which contribute additionally to the metabolic phenotypes generated. These observations have clinical and public health implications.
 ...
PMID:Complement C3 and cleavage products in cardiometabolic risk. 2141 12

Our objective was to evaluate the association of plasma inflammatory biomarkers with MetS in an older population of treated HIV-infected (HIV(+)) as compared to age-matched HIV-negative (HIV(-)) adults. This was done in a retrospective observational study. Plasma concentrations of complement component 3 (C3), cystatin C, fibroblast growth factor 1, interleukin 6, oxidized LDL, soluble RAGE, soluble CD163, soluble CD14, and osteopontin were measured in 79 HIV(+) participants on combination antiretroviral treatment (cART) with a suppressed HIV viral load and 47 HIV(-) participants with a median age of 59 (range 50 to 79). Outcomes were individual MetS components (hypertension, type II diabetes, dyslipidemia, and obesity) and MetS. Covariates were screened for inclusion in multivariable models. Odds ratios are reported per 50 mg/dl increase in C3. In the HIV(+) group, higher C3 levels were associated with MetS (OR 3.19, p = 0.004), obesity (OR 2.02, p = 0.01), type II diabetes (OR 1.93, p = 0.02), and at a trend level with dyslipidemia (OR 1.87, p = 0.07) and hypertension (OR 1.66, p = 0.09). C3 levels were significantly higher in HIV(+) participants with MetS compared to those without MetS (p = 0.002). C3 was higher among HIV(+) patients with three or four MetS components as compared to those with one or two (p = 0.04) and those with none (p = 0.002). No associations were found between C3 and the outcomes for HIV(-) participants. C3 is strongly associated with both MetS and MetS components in an older HIV(+) sample on cART compared to HIV(-) controls. C3 warrants further investigation as a marker of cardiometabolic risk among persons aging with HIV.
 ...
PMID:Complement Component 3 Is Associated with Metabolic Comorbidities in Older HIV-Positive Adults. 2649 82