8-epi-prostaglandin-f2alpha and Weight-Loss

The objective of this study was to test the hypothesis that the inflammatory response to a high-fat, low-carbohydrate weight loss diet (HF) we previously observed was due to oxidative stress. Nineteen overweight subjects (BMI>27 kg/m(2)) were randomly assigned to either an antioxidant supplement (AS) (1 g vitamin C/800 IU vitamin E) or a placebo (P) group and provided with a HF for 7 days. Fasted pre- and post serum samples were measured for markers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1)), oxygen radical absorbance capacity (ORAC), and glucose, whereas urine was measured for oxidative stress (8-epi-prostaglandin-F(2alpha) (8-epi)). HF resulted in significant reductions in weight (-3.2%), glucose (-18.7%), and MCP-1 (-15%) (all P<0.01), with no difference between groups. There was a trend for a differential effect between groups for CRP as it decreased 32% in the AS group but increased 50% for P (P=0.076). Inverse correlations were noted between initial values and changes in several inflammatory and oxidative stress markers, including CRP (r= -0.501), 8-epi (r= -0.863), and ORAC (r= -0.546) (all P<0.05). It was concluded that weight loss on a short-term HF caused reduction of some but not all markers of inflammation. A role for oxidative stress in causing inflammation was not confirmed; however, longer term diet-controlled studies are necessary to further explore the trend for a differential response in CRP with antioxidant supplementation.

Topics: Antioxidants; Ascorbic Acid; Biomarkers; Blood Glucose; C-Reactive Protein; Chemokine CCL2; Diet, Carbohydrate-Restricted; Dietary Fats; Dinoprost; Drug Combinations; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Male; Obesity; Oxidative Stress; Reactive Oxygen Species; Time Factors; Treatment Outcome; Vitamin E; Weight Loss

Obesity is associated with increased levels of inflammatory mediators. The objective of this study was to evaluate changes in the leucocyte derived inflammatory mediators tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and the isoprostane 8-epi-prostaglandin (PG) F2alpha during BMI lowering with orlistat (Xenical(R), Roche) or placebo.. TNF-alpha, IL-6, and 8-epi PGF2alpha evaluated in 376 subjects aged 18-75 years with BMI 28-38 kg/m2 before and after 1 year of double-blind, randomized treatment with orlistat 120 mg or placebo three times daily.. Weight reduction was associated with decreasing (p < 0.001) levels of TNF-alpha and IL-6 in both orlistat and placebo groups. After 12 months, TNF-alpha was lower (p < 0.05) in the orlistat compared with the placebo group. In the orlistat group, the change in TNF-alpha correlated with change in s-glucose (r = 0.22; p = 0.01), and the change in 8-epi-PGF2alpha correlated with changes in s-cholesterol (r = 0.27; p < 0.001) and s-LDL-cholesterol (r = 0.28; p < 0.001).. Weight reduction was associated with decreasing levels of both TNF-alpha and IL-6. After 12 months of treatment, TNF-alpha levels were lower in orlistat than in placebo-treated subjects. Whether these results translate into reduced incidence of cardiovascular disease remains to be elucidated.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Body Mass Index; Cardiovascular Diseases; Dinoprost; Double-Blind Method; Female; Follow-Up Studies; Humans; Interleukin-6; Lactones; Lipids; Male; Middle Aged; Obesity; Orlistat; Risk Factors; Tumor Necrosis Factor-alpha; Weight Loss

Obesity-induced oxidative stress and inflammation are involved in the pathogenesis of cardiovascular disease. We investigated whether diet-induced, long-term, mild weight loss improved proinflammatory cytokine levels, leukocyte count, and oxidative stress. Overweight/obese participants (25 ≤ body mass index < 34 kg/m(2), N = 122, 30-59 years) joined a 3-year-long clinical intervention involving daily 100-kcal calorie deficits. Successful weight loss was defined as a reduction in initial body weight equal to 2 kg after the clinical intervention period. Body weight in the successful mild weight loss group (SWL, n = 50) changed 5.4% (-4.16 ± 0.31 kg) compared to 0.05 ± 0.14 kg in the unsuccessful weight loss group (n = 49). After 3 years, SWL participants exhibited significantly reduced insulin, triglycerides, total and low-density lipoprotein cholesterol, free fatty acids, and leukocyte count (P = .030). Furthermore, in the SWL group, serum interleukin (IL)-1β, IL-6, and urinary 8-epi-prostaglandin (PG)F2α were significantly reduced (45%, 30%, and 14%, respectively). In contrast, the unsuccessful weight loss group exhibited significant increases in percentage of body fat, waist circumference, oxidized low-density lipoprotein, and tumor necrosis factor-α, as well as a significant decrease in high-density lipoprotein cholesterol. After adjusting for baseline values, the 2 groups demonstrated significantly different percentage of body fat, waist circumference, leukocyte count (P = .018), insulin, IL-6 (P = .031), IL-1β (P < .001), and tumor necrosis factor-α (P < .001), as well as urinary 8-epi-PGF2α (P = .036). A positive correlation existed between IL-1β and urinary 8-epi-PGF2α (r = 0.435, P < .001) and between changes in IL-6 and urinary 8-epi-PGF2α (r = 0.393, P < .001). Long-term mild weight loss reduces inflammatory cytokine levels, leukocyte counts, and oxidative stress and may reverse the elevated oxidative stress induced by inflammatory mediators in the overweight and obese.

Topics: Adiposity; Adult; Body Mass Index; Cytokines; Diet, Reducing; Dinoprost; Female; Humans; Inflammation; Insulin; Interleukin-1beta; Interleukin-6; Leukocyte Count; Lipids; Male; Middle Aged; Obesity; Overweight; Oxidative Stress; Tumor Necrosis Factor-alpha; Waist Circumference; Weight Loss

The receptor for advanced glycation end-products (RAGE) has been implicated in obesity-related metabolic disease and accelerated atherothrombosis.. We tested the hypothesis that changes in endogenous secretory (es)RAGE levels as a result of excess adiposity and oxidative stress may contribute to enhancing platelet activation in obese women, thus increasing the cardiovascular risk.. Eighty otherwise healthy obese women and 20 nonobese women were studied.. esRAGE and plasma adiponectin were reduced in obese women [median (interquartile range), 0.18 (0.13-0.26) vs. 0.38 (0.20-0.48) ng/ml, P = 0.003; and 4.4 (2.8-6.4) vs. 10.0 (6.9-12.5) μg/ml, P < 0.0001, respectively] who also displayed higher urinary 11-dehydro-thromboxane B(2) (11-dehydro-TXB(2)) [795 (572-1089) vs. 211 (135-301) pg/mg creatinine; P < 0.0001] and 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)) [544 (402-698) vs. 149 (98-219) pg/mg creatinine; P < 0.0001] compared to nonobese women. Direct correlations between plasma adiponectin and esRAGE (Rho = 0.43; P < 0.0001) and between urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2) (Rho = 0.36; P = 0.001) were observed in obese women. Moreover, plasma esRAGE and urinary 11-dehdro-TXB(2) were inversely related (Rho = -0.29; P = 0.008). On multiple linear regression analysis, urinary 8-iso-PGF(2α) and plasma esRAGE were independent predictors of urinary 11-dehydro-TXB(2). In five obese women, a short-term weight loss program gave a significant increase in esRAGE and decrease in urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2).. In otherwise healthy obese women, low plasma esRAGE levels are associated with reduced circulating adiponectin and enhanced thromboxane biosynthesis, which is in part mediated by increased lipid peroxidation. Thus, excess adiposity may be implicated in RAGE hyperactivation and thromboxane-dependent platelet activation, contributing to obesity-related metabolic and vascular disease.

Topics: Adiponectin; Adult; Anthropometry; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Dinoprost; Female; Humans; Linear Models; Lipid Peroxidation; Lipids; Middle Aged; Obesity; Oxidative Stress; Platelet Activation; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Risk; Thromboxane B2; Weight Loss

Excessive fat deposition is the key feature in obesity, which is empowered by cytokines overproduction and stimulation of cell oxidative stress processes, but little is known about energy availability in the form of ATP and mitochondrial function in the obese subjects. Thus, the aim of this study was to evaluate the possible changes in energy metabolism after a 8-weeks balanced-hypocaloric diet in obese subjects by measuring the ATP-content in leukocytes, by assessing 2-keto[1-13C]isocaproate breath test (KICA-BT) parameters related to mitochondrial function and by analyzing inflammatory and oxidative stress biomarkers. All the recruited obese subjects (n = 19) lost body weight after dieting (-5.55 +/- 2.88%). The hypocaloric treatment induced a decrease in leptin levels and lipid peroxidation markers. Interestingly, the ATP content in blood leukocytes increased (49.9 +/- 32.5 vs 36.2 +/- 27.9 pmol/mg prot.; p < 0.05), while KICA tracer mitochondrial oxidation decreased (30.9 +/- 5.9 vs. 33.1 +/- 4.5 % 13C; p < 0.05) after weight loss. These results show that two minimally invasive methods were able to detect changes in mitochondrial function as induced by a hypocaloric diet, which is of great interest in order to understand oxidative processes associated with weight homeostasis as well as to establish newer anti-obesity therapeutic targets by using mitochondrial function markers in vivo.

Topics: Adenosine Triphosphate; Adult; Biomarkers; Breath Tests; C-Reactive Protein; Caloric Restriction; Dinoprost; Energy Metabolism; Female; Humans; Interleukin-6; Keto Acids; Leukocytes; Male; Malondialdehyde; Mitochondria; Obesity; Oxidative Stress; Weight Loss

Topics: CD40 Ligand; Dinoprost; F2-Isoprostanes; Humans; Male; Middle Aged; Obesity; Platelet Activation; Weight Loss