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

• Published in: American journal of hypertension Vol. 20; no. 2; pp. 206 - 210
• Main Authors: Sharabi, Yehonatan, Oron-Herman, Mor, Kamari, Yehuda, Avni, Irit, Peleg, Edna, Shabtay, Zehava, Grossman, Ehud, Shamiss, Arie
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-02-2007; Oxford University Press; Elsevier Science
• Subjects: adiponectin; Adiponectin - blood; Adiponectin - genetics; Adiponectin - metabolism; Adipose Tissue - chemistry; Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Diet; Disease Models, Animal; Experimental diseases; Fructose - administration & dosage; Glucose Tolerance Test; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Insulin - blood; Male; Medical sciences; Metabolic syndrome; Metabolic Syndrome - chemically induced; Metabolic Syndrome - drug therapy; PPAR gamma; PPAR gamma - agonists; Rats; Rats, Sprague-Dawley; RNA, Messenger - analysis; RNA, Messenger - metabolism; rosiglitazone; Thiazolidinediones - pharmacology; Thiazolidinediones - therapeutic use; Triglycerides - blood; Up-Regulation; adiponectin; rosiglitazone; Metabolic syndrome; PPAR gamma; Hypertension; Rat; Rodentia; Cardiovascular disease; Thiazolidinedione derivatives; Fructose; Vertebrata; Hypoglycemic agent; Mammalia; Animal; Rosiglitazone
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/j.amjhyper.2006.08.002

The health hazard of the metabolic syndrome (MS) is increasing, yet there is no effective pharmacologic treatment to this entity as a whole. Recently, hypoadiponectinemia was found to play an important role in the development of MS. We studied the effect of the PPAR-γ agonist rosiglitazone on adiponectin and the metabolic profile in the fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic rat model.
Thirty male Sprague-Dawley rats were divided into three groups. Ten were fed standard rat chow for 5 weeks, 10, a fructose-enriched diet for 5 weeks, and 10, a fructose-enriched diet for 5 weeks, with rosiglitazone 10 mg/kg/d added during the last 2 weeks. Blood pressure (BP), oral glucose tolerance test (OGTT), plasma insulin, triglycerides, and adiponectin were recorded, as well as mRNA levels of the adiponectin gene in visceral adipose tissue.
Fructose-fed rats developed MS as manifested by the increase in systolic BP (from 139 ± 3 to 158 ± 4 mm Hg,
P < .05), insulin (from 26 ± 1.6 to 40 ± 2.5 μU/mL,
P < .05), triglycerides (from 91 ± 9 to 304 ± 24 mg/dL,
P < .05), and impaired OGTT (area under the curve from 13,894 ± 246 to 17,725 ± 700 mg/dL/min). Treatment with rosiglitazone reversed these effects and reduced BP to 133 ± 7 mm Hg, insulin levels to 30 ± 2.8 μU/mL, triglycerides to 116 ± 9 mg/dL, and the OGTT to 15,415 ± 372 mg/dL/min (
P < .05 for all variables). In addition, rosiglitazone increased plasma levels of adiponectin fourfold from 4.3 ± 0.1 to 18.4 ± 0.6 μg/mL (
P < .05). This increase was coupled with 3.8-fold increase in adiponectin mRNA in visceral adipose tissue.
This study shows for the first time that in an animal model of MS, the insulin sensitizer, rosiglitazone, improves the metabolic profile and increases plasma levels of adiponectin and its gene expression. It is possible therefore that rosiglitazone exerts its beneficial effects by increasing the levels of adiponectin.