Associations between hypertriglyceridemia and serum ghrelin, adiponectin, and IL-18 levels in HIV-infected patients.

HIV-related metabolic abnormalities include hypertriglyceridemia, hypercholesterolemia, insulin resistance, and diabetes mellitus. Recent studies suggest a role of ghrelin in promoting the deposition of triglycerides (TG) in the liver and regulating the metabolic action of adiponectin. Visceral fat is a key regulator of inflammation and it secretes proinflammatory cytokines (eg, interleukin-18, IL-18), with potential atherogenic activity. The aim of this study was to assay serum concentrations of ghrelin, adiponectin, and IL-18 in HIV+ patients, with and without hypertriglyceridemia, who were receiving highly active antiretroviral therapy (HAART). The 49 HIV+ patients were divided in 2 groups: 17 patients with serum TG concentration >200 mg/dl (group A) and 32 patients with normal serum TG concentration (group B). All subjects underwent viral and immunological evaluations and determinations of serum cholesterol, glucose, ghrelin, adiponectin, and IL-18. No differences of viral and immunological parameters were observed between the 2 groups. Serum levels of ghrelin were 768 +/- 596 pg/dl in group A and 470 +/- 248 pg/dl in group B (p = 0.01). Group A had lower serum adiponectin levels (8.4 +/- 3.6 microg/dl) than group B (18.2 +/- 10.1 microg/dl; p = 0.0001). Serum IL-18 levels were 455 +/- 199 pg/ml in group A and 258 +/- 233 pg/ml in group B (p = 0.005). The patients with hypertriglyceridemia showed a positive correlation between serum triglyceride and ghrelin levels (r = 0.51, p = 0.03). These findings suggest potential roles of ghrelin, adiponectin, and IL-18 in the pathogenesis of metabolic disorders in HIV-infected patients.

Association between plasma interleukin-18 levels and liver injury in chronic hepatitis C virus infection and non-alcoholic fatty liver disease.

There is significant upregulation of interleukin-18 (IL-18) expression in viral infectious diseases and in some chronic hepatic diseases, especially (i) hepatitis C virus (HCV) infection, (ii) HCV infection with persistently normal ALT levels (PNAL), and (iii) non-alcoholic fatty liver disease (NAFLD). The aim of this study was a better understanding of the implications of plasma IL-18 levels in the above-mentioned liver diseases. Thirty-four patients with HCV infection, 13 with NAFLD, and 10 controls were enrolled. The HCV-RNA and HCV-genotypes and the serum or plasma levels of IL-18, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (gamma-GT), alkaline phosphatase, total cholesterol, triglycerides, alpha(1)-fetoprotein, and ferritin were evaluated. Patients with HCV showed higher levels of IL-18 than the NAFLD patients (p <0.01) and the controls (p <0.005). Patients with NAFLD showed higher values of body mass index and liver disease parameters, compared to HCV-infected subjects or controls. These data confirm previous reports of enhanced expression of IL-18 in patients with HCV and NAFLD, compared to healthy subjects, and suggest that IL-18 is important as a marker of liver diseases.

Association of inflammation markers with impaired insulin sensitivity and coagulative activation in obese healthy women.

Insulin resistance is associated with a low chronic inflammatory state. In this study we investigated the relationship between impaired insulin sensitivity and selected markers of inflammation and thrombin generation in obese healthy women. We examined 32 healthy obese women (body mass index > or = 28), with normal insulin sensitivity (NIS, n = 14) or impaired insulin sensitivity (n = 18), and 10 nonobese women (body mass index < 25). Impaired insulin sensitivity patients had significantly higher levels of C-reactive protein (CRP), TGF-beta 1, plasminogen activator inhibitor-1 (PAI-1), activated factor VII (VIIa), and prothrombin fragment 1 + 2 (F1 + 2) compared with either control subjects or NIS patients. On the other hand, NIS patients had higher CRP, TGF-beta 1, PAI-1, and factor VIIa, but not F1 + 2, levels than controls. Significant inverse correlations were observed between the insulin sensitivity index and TGF-beta 1, CRP, PAI-1, factor VIIa, and F1 + 2 levels. Moreover, significant direct correlations were noted between TGF-beta 1 and CRP, PAI-1, factor VIIa, and F1 + 2 concentrations. Finally, multiple regressions revealed that TGF-beta 1 and the insulin sensitivity index were independently related to F1 + 2. Our results are the first to document an in vivo relationship between insulin sensitivity and coagulative activation in obesity. The elevated TGF-beta 1 levels detected in the obese population may provide a biochemical link between insulin resistance and an increased risk for cardiovascular disease.

Association between serum leptin levels and 24-hour blood pressure in obese women.

OBJECTIVE: To assess the relationship between serum leptin and 24-hour blood pressure (BP) in obese women, according to body fat distribution. RESEARCH METHODS AND PROCEDURES: A cross-sectional study was carried out in a population of 70 nondiabetic, normotensive, obese women (40 with android and 30 with gynoid type of obesity) and 20 nonobese healthy women as a control group. All subjects underwent 24-hour ambulatory BP monitoring. Blood samples were collected for serum leptin and plasma insulin measurements. Total cholesterol and high-density lipoprotein cholesterol were also measured. RESULTS: Serum leptin levels were significantly higher in obese subjects than in controls, and they were more elevated in android obese women than in gynoid ones. Leptin levels were positively related to body mass index (BMI), insulin, and waist and hip circumferences in the android group. Among gynoid subjects, leptin levels showed positive associations with BMI and insulin. In women with android obesity, strong positive correlations (p < 0.001) were found between leptin levels and 24-hour systolic BP (SBP), daytime SBP, nighttime SBP, 24-hour diastolic BP (DBP), and daytime DBP. Multiple regression analyses, including age, insulin and leptin concentrations, BMI, and waist and hip circumferences on 24-hour and daytime SBP and DBP, showed that only leptin levels contributed to the variability of BP. CONCLUSIONS: Our study shows that serum leptin levels are directly related to 24-hour BP levels in normotensive women with android fat distribution, independently of BMI.

Platelet activation in obese women: role of inflammation and oxidant stress.

CONTEXT: Obesity, in particular abdominal adiposity, is associated with increased cardiovascular morbidity and mortality through mechanisms possibly linking the metabolic disorder to platelet and vascular abnormalities. OBJECTIVE: To investigate the clinical and biochemical determinants of lipid peroxidation and platelet activation in obese women. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional comparison, conducted between September 1999 and September 2001, of urinary 8-iso prostaglandin F(2alpha) (8-iso PGF(2alpha)) and 11-dehydrothromboxane B2 (11-dehyhdro-TxB2) excretion levels in 93 women: 44 with a body mass index (BMI) higher than 28 and a waist-to-hip ratio (WHR) of 0.86 or higher, android obesity; 25 with a BMI higher than 28 and a WHR lower than 0.86, gynoid obesity; and 24 nonobese women with a BMI lower than 25. An additional study was conducted to determine the short-term effects of weight loss in 20 of the 44 women with android obesity. INTERVENTION: During a 12-week period, 20 women with android obesity followed a weight loss program to reduce caloric intake to about 1200 kcal/d. MAIN OUTCOME MEASURES: Plasma C-reactive protein, insulin and leptin levels, and urinary 8-iso PGF(2alpha) (marker of in vivo lipid peroxidation) and 11-dehyhdro-TxB2 (marker of in vivo platelet activation) excretion. Weight loss was defined as successful when the initial body weight decreased by at least 5 kg after a 12-week period of caloric restriction. RESULTS: Women with android obesity had higher levels of 8-iso PGF(2alpha )(median [interquartile range [IQR]] 523 [393-685] vs 187 [140-225] pg/mg creatinine) and 11-dehyhdro-TxB2 (median [IQR], 948 [729-1296] vs 215 [184-253] pg/mg creatinine) than nonobese women (P<.001). Both 8-iso PGF(2alpha)and 11-dehyhdro-TxB2 were higher in women with android obesity than women with gynoid obesity (P<.001). Based on multiple regression analysis, C-reactive protein levels and WHRs of 0.86 or higher predicted the rate of 8-iso PGF(2alpha) excretion independently of insulin and leptin levels. Of 20 women with android obesity, 11 achieved successful weight loss, which was associated with statistically significant reductions in C-reactive protein (median change, 23%; P<.05), 8-iso PGF(2alpha) (median change, 32%; P =.04) and 11-dehydro-TxB2 (median change, 54%; P =.005). CONCLUSIONS: Android obesity is associated with enhanced lipid peroxidation and persistent platelet activation. These abnormalities are driven by inflammatory triggers related to the degree of abdominal adiposity and are, at least in part, reversible with a successful weight-loss program.