18
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Effects of Endogenous PPAR Agonist Nitro-Oleic Acid on Metabolic Syndrome in Obese Zucker Rats

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Nitroalkene derivatives of nitro-oleic acid (OA-NO 2) are endogenous lipid products with novel signaling properties, particularly the activation of PPARs. The goal of this proposal was to examine the therapeutic potential of this OA-NO 2 in treatment of obesity and obesity-related conditions in obese Zucker rats. The animals were randomly divided to receive OA-NO 2, oleic acid (OA), both at 7.5  μg/kg/d, or vehicle ethanol via osmotic mini-pumps for 2 weeks. Following OA-NO 2 treatment, food intake was decreased as early as the first day and this effect appeared to persist throughout the experimental period. At day 14, body weight gain was significantly reduced by OA-NO 2 treatment. This treatment significantly reduced plasma triglyceride and almost normalized plasma free fatty acid and significantly increased plasma high-density lipid (HDL). The plasma TBARS and proteinuria were paralelly decreased. In contrast, none of these parameters were affected by OA treatment. After 14 days of OA-NO 2 treatment, hematocrit, a surrogate of fluid retention associated with PPAR γ agonists, remained unchanged. Together, these data demonstrated that OA-NO 2 may offer an effective and safe therapeutic intervention for obesity and obesity-related conditions.

          Related collections

          Most cited references42

          • Record: found
          • Abstract: found
          • Article: not found

          Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials.

          Since the prevalence of obesity continues to increase, there is a demand for effective and safe anti-obesity agents that can produce and maintain weight loss and improve comorbidity. We did a meta-analysis of all published randomised controlled trials to assess the efficacy and safety of the newly approved anti-obesity agent rimonabant. We searched The Cochrane database and Controlled Trials Register, Medline via Pubmed, Embase via WebSpirs, Web of Science, Scopus, and reference lists up to July, 2007. We collected data from four double-blind, randomised controlled trials (including 4105 participants) that compared 20 mg per day rimonabant with placebo. Patients given rimonabant had a 4.7 kg (95% CI 4.1-5.3 kg; p<0.0001) greater weight reduction after 1 year than did those given placebo. Rimonabant caused significantly more adverse events than did placebo (OR=1.4; p=0.0007; number needed to harm=25 individuals [95% CI 17-58]), and 1.4 times more serious adverse events (OR=1.4; p=0.03; number needed to harm=59 [27-830]). Patients given rimonabant were 2.5 times more likely to discontinue the treatment because of depressive mood disorders than were those given placebo (OR=2.5; p=0.01; number needed to harm=49 [19-316]). Furthermore, anxiety caused more patients to discontinue treatment in rimonabant groups than in placebo groups (OR=3.0; p=0.03; number needed to harm=166 [47-3716]). Our findings suggest that 20 mg per day rimonabant increases the risk of psychiatric adverse events--ie, depressed mood disorders and anxiety-despite depressed mood being an exclusion criterion in these trials. Taken together with the recent US Food and Drug Administration finding of increased risk of suicide during treatment with rimonabant, we recommend increased alertness by physicians to these potentially severe psychiatric adverse reactions.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Dietary fat, insulin sensitivity and the metabolic syndrome.

            Insulin resistance is the pathogenetic link underlying the different metabolic abnormalities clustering in the metabolic syndrome. It can be induced by different environmental factors, including dietary habits. Consumption of energy-dense/high fat diets is strongly and positively associated with overweight that, in turn, deteriorates insulin sensitivity, particularly when the excess of body fat is located in abdominal region. Nevertheless the link between fat intake and overweight is not limited to the high-energy content of fatty foods; the ability to oxidize dietary fat is impaired in some individuals genetically predisposed to obesity. Insulin sensitivity is also affected by the quality of dietary fat, independently of its effects on body weight. Epidemiological evidence and intervention studies clearly show that in humans saturated fat significantly worsen insulin-resistance, while monounsaturated and polyunsaturated fatty acids improve it through modifications in the composition of cell membranes which reflect at least in part dietary fat composition. A recent multicenter study (KANWU) has shown that shifting from a diet rich in saturated fatty acids to one rich in monounsaturated fat improves insulin sensitivity in healthy people while a moderate alpha-3 fatty acids supplementation does not affect insulin sensitivity. There are also other features of the metabolic syndrome that are influenced by different types of fat, particularly blood pressure and plasma lipid levels. Most studies show that alpha-3 fatty acids reduce blood pressure in hypertensive but not in normotensive subjects while shifting from saturated to monounsaturated fat intake reduces diastolic blood pressure. In relation to lipid abnormalities alpha-3 fatty acids reduce plasma triglyceride levels but in parallel, increase LDL cholesterol. Substitution of unsaturated fat for saturated fat not only reduces LDL cholesterol but contributes also to reduce plasma triglycerides in insulin resistant individuals. In conclusion, there is evidence available in humans indicating that dietary fat quality influences insulin sensitivity and associated metabolic abnormalities. Therefore, prevention of the metabolic syndrome has to be targeted: (1) to correct overweight by reducing the energy density of the habitual diet (i.e., fat intake) and (2) to improve insulin sensitivity and associated metabolic abnormalities through a reduction of dietary saturated fat, partially replaced, when appropriate, by monounsaturated and polyunsaturated fats. Copyright 2004 Elsevier Ltd.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              PPAR delta: a dagger in the heart of the metabolic syndrome.

              Obesity is a growing threat to global health by virtue of its association with insulin resistance, glucose intolerance, hypertension, and dyslipidemia, collectively known as the metabolic syndrome or syndrome X. The nuclear receptors PPARalpha and PPARgamma are therapeutic targets for hypertriglyceridemia and insulin resistance, respectively, and drugs that modulate these receptors are currently in clinical use. More recent work on the less-described PPAR isotype PPARdelta has uncovered a dual benefit for both hypertriglyceridemia and insulin resistance, highlighting the broad potential of PPARdelta in the treatment of metabolic disease. PPARdelta enhances fatty acid catabolism and energy uncoupling in adipose tissue and muscle, and it suppresses macrophage-derived inflammation. Its combined activities in these and other tissues make it a multifaceted therapeutic target for the metabolic syndrome with the potential to control weight gain, enhance physical endurance, improve insulin sensitivity, and ameliorate atherosclerosis.
                Bookmark

                Author and article information

                Journal
                PPAR Res
                PPAR
                PPAR Research
                Hindawi Publishing Corporation
                1687-4757
                1687-4765
                2010
                5 July 2010
                : 2010
                : 601562
                Affiliations
                1Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah, 30 N 1900 E, Rm 4R312, Salt Lake City, UT 84132, USA
                2Department of Nephrology, 2nd Affiliated Hospital, Shandong University, Jinan, China
                Author notes

                Academic Editor: Nanping Wang

                Article
                10.1155/2010/601562
                2910468
                20671947
                f7a8586d-8561-4d4b-9860-9e8b0e91d051
                Copyright © 2010 Haiping Wang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 5 February 2010
                : 29 April 2010
                : 8 May 2010
                Categories
                Research Article

                Biochemistry
                Biochemistry

                Comments

                Comment on this article

                scite_

                Similar content277

                Cited by9

                Most referenced authors765