Effect of PPAR-γ Agonist on Adiponectin Levels in the Metabolic Syndrome: Lessons From the High Fructose Fed Rat Model

Sharabi, Yehonatan; Oron‐Herman, Mor; Kamari, Yehuda; Avni, Irit; Peleg, Edna; Shabtay, Zehava; Grossman, Ehud; Shamiss, Ari

doi:10.1016/j.amjhyper.2006.08.002

Cited by 87 publications

(63 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, telmisartan did not affect plasma adiponectin, a protein whose levels are known to increase with existing PPARγ agonists and to correlate with insulin sensitivity (23)(24)(25)(26). We recently showed in fructose fed rats that the PPARγ agonist rosiglitazone improved the metabolic profile to a degree similar to telmisartan, but with increases in plasma adiponectin levels and gene expression (15). Therefore, it is unlikely that adiponectin mediates telmisartan's beneficial effect on metabolic parameters.…”

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Effect of Telmisartan, Angiotensin II Receptor Antagonist, on Metabolic Profile in Fructose-Induced Hypertensive, Hyperinsulinemic, Hyperlipidemic Rats

et al. 2008

View full text Add to dashboard Cite

The metabolic syndrome (MS) is a common risk factor for cardiovascular disease and type-2 diabetes.Recently, telmisartan, an angiotensin II receptor antagonist that has an antihypertensive effect, has been reported to be a partial peroxisome proliferator-activated receptor (PPAR ) agonist. The anti-diabetic hormone adiponectin has been recognized as a marker of in vivo PPAR activation. Therefore, we studied telmisartan's effect on the metabolic profile and adiponectin levels in a fructose-induced hypertensive, hyperinsulinemic, hyperlipidemic rat model. Twenty-four male Sprague-Dawley rats were divided into three groups (eight in each). One group of control rats was fed standard chow for 5 weeks while a second was fed a fructose-enriched diet. A third group was fed a fructose-enriched diet for 5 weeks and treated with telmisartan 5 mg/kg/day during the last 2 weeks. Fructose feeding increased systolic blood pressure (mean± SEM), from 130 ± 1 to 148 ± 2 mmHg, insulin from 0.26 ± 0.03 to 0.68 ± 0.08 ng/mL, and triglycerides from 102 ± 6 to 285 ± 23 mg/dL ( p < 0.05 for all variables). Telmisartan treatment reversed these effects and reduced blood pressure to 125 ± 2 mmHg, insulin levels to 0.41 ± 0.07 ng/mL, and triglycerides to 146 ± 18 mg/dL ( p < 0.05 for all variables), while attenuating the increase in body weight during weeks 3 to 5. In contrast, telmisartan did not affect plasma adiponectin levels. In conclusion, although telmisartan is considered a partial PPAR agonist, its beneficial effect in the fructose-induced hypertension, hypertriglyceridemia, and hyperinsulinemia rat model is apparently not mediated by adiponectin elevation but rather by direct inhibi-

show abstract

Section: Discussionmentioning

confidence: 96%

“…Accumulating data have shown that PPARγ activation increases adiponectin levels (14,15). Recent studies suggested that telmisartan, an angiotensin II receptor antagonist, is also a partial PPARγ agonist (16,17).…”

Section: Discussionmentioning

confidence: 99%

Effect of Telmisartan, Angiotensin II Receptor Antagonist, on Metabolic Profile in Fructose-Induced Hypertensive, Hyperinsulinemic, Hyperlipidemic Rats

et al. 2008

View full text Add to dashboard Cite

show abstract

“…15 To determine the role of Treg in the metabolic syndrome, vascular oxidative stress and inflammation and the number and function of Treg were studied in high-fructose diet-fed SpragueDawley rats, a well-established model mimicking some features of the western diet-induced metabolic syndrome. 16,17 These rats exhibit hypertension, insulin resistance, and abnormal lipid profile resembling the human metabolic syndrome better than a monogenic model. We hypothesized that vascular oxidative stress and inflammation and changes in the immune response, including Treg activity and response, participate in the mechanisms leading to the metabolic syndrome.…”

Section: Foxp3mentioning

confidence: 99%

“…16,17 These rats exhibit hypertension, insulin resistance, and abnormal lipid profile resembling the human metabolic syndrome better than a monogenic model. We hypothesized that vascular oxidative stress and inflammation and changes in the immune response, including Treg activity and response, participate in the mechanisms leading to the metabolic syndrome.…”

mentioning

confidence: 99%

Role of T Regulatory Lymphocytes in the Pathogenesis of High-Fructose Diet–Induced Metabolic Syndrome

et al. 2013

View full text Add to dashboard Cite

Abstract-We recently showed that T regulatory lymphocytes (Treg), which are immune suppressors of inflammatory responses, play a role blunting the development of hypertension-induced injury. Treg are unchanged or decreased in children with metabolic syndrome, and therefore, their role in metabolic syndrome remains unclear. We hypothesized that Treg number or function would be depressed in a high-fructose diet-induced metabolic syndrome-like model in rats. Sprague-Dawley rats were fed normal chow or a high-fructose diet for 5 weeks. The high-fructose diet-induced a 3.8-fold increase in plasma triglycerides and a 14% reduction in high-density lipoprotein cholesterol (P<0.001). The high-fructose diet increased reactive oxygen species in aorta and periaortic adipose tissue 2.8-fold (P<0.05), and reduced nicotinamide adenine dinucleotide phosphate oxidase activity 1.9-fold in aorta, and 2.5-fold in the heart (P<0.05). It also increased plasma nitric oxide metabolite levels 6.4-fold (P<0.001). Western blots showed that the high-fructose diet increased ≥2.3-fold vascular and in platelet endothelial cell adhesion molecule 1 in aorta (P<0.01). It did not affect monocyte/macrophage aortic infiltration but caused a 2.4-fold increase in collagen deposition in the aortic media (P<0. 01 FoxP3+ cells was observed in children with metabolic syndrome (2.5 versus 3.1%). 15To determine the role of Treg in the metabolic syndrome, vascular oxidative stress and inflammation and the number and function of Treg were studied in high-fructose diet-fed SpragueDawley rats, a well-established model mimicking some features of the western diet-induced metabolic syndrome. 16,17 These rats exhibit hypertension, insulin resistance, and abnormal lipid profile resembling the human metabolic syndrome better than a monogenic model. We hypothesized that vascular oxidative stress and inflammation and changes in the immune response, including Treg activity and response, participate in the mechanisms leading to the metabolic syndrome. Materials and MethodsAdditional materials and methods are described in the online-only Data Supplement. Experimental DesignEight-week-old Sprague-Dawley male rats (Harlan Laboratories, Indianapolis, IN) were fed a high-fructose diet (TD.89247, Harlan Laboratories) composed of 60% fructose, 21% protein, 5% fat, 8% cellulose, and standard vitamins and mineral mix or normal chow diet (control) for 5 weeks. Systolic BP (SBP) was measured by the tailcuff method after 4 weeks on the diet. SBP was also determined by telemetry together with heart rate and animal activity every 5 minutes for 10 seconds for 2 consecutive days at baseline and at the end of every week during the 5 weeks of treatment. Three days before the end of the protocol, blood was collected from the saphenous vein on heparin for triglycerides, and high-density lipoprotein cholesterol was determined after 5 hours of fasting. At the end of the protocol, body weight was evaluated, and rats were anesthetized with 3% isoflurane mixed with O 2 at 1 L/min (depth of ane...

show abstract

“…However, the underlying mechanisms remain controversial. Some studies report that adiponectin mRNA levels are increased after PPAR␥ agonist treatment but others do not (14,15). It is likely that PPAR␥ may exert its primary effect on adiponectin secretion by providing a more productive folding environment (2, 5) through transcriptional up-regulation of critical ER chaperones, including ERp44, Ero1-L␣ and DsbA-L, which may thus lead to a stimulation of assembly and release of the HMW form.…”

Section: Transcriptional Vs Posttranslational Roles Of Ppar␥ Activatmentioning

confidence: 99%

DsbA-L is a versatile player in adiponectin secretion

Wang

Scherer

2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Effect of PPAR-γ Agonist on Adiponectin Levels in the Metabolic Syndrome: Lessons From the High Fructose Fed Rat Model

Cited by 87 publications

References 30 publications

Effect of Telmisartan, Angiotensin II Receptor Antagonist, on Metabolic Profile in Fructose-Induced Hypertensive, Hyperinsulinemic, Hyperlipidemic Rats

Effect of Telmisartan, Angiotensin II Receptor Antagonist, on Metabolic Profile in Fructose-Induced Hypertensive, Hyperinsulinemic, Hyperlipidemic Rats

Role of T Regulatory Lymphocytes in the Pathogenesis of High-Fructose Diet–Induced Metabolic Syndrome

DsbA-L is a versatile player in adiponectin secretion

Contact Info

Product

Resources

About