A novel PPARalpha agonist ameliorates insulin resistance in dogs fed a high-fat diet

American Journal of Physiology. Endocrinology and Metabolism
Masaki TsunodaKoji Murakami

Abstract

Agonism of peroxisome proliferator-activated receptor (PPAR) alpha, a key regulator of lipid metabolism, leads to amelioration of lipid abnormalities in dyslipidemic patients. However, whether PPARalpha agonism is an effective form of therapy for obesity-related insulin resistance associated with lipid abnormalities is unclear. The present study investigated the effects of a potent and subtype-selective PPARalpha agonist, KRP-101, in a nonrodent insulin-resistant animal model under pair-fed conditions. Beagle dogs were fed a high-fat diet for 24 wk to induce insulin resistance. During the final 12 wk, 0.03 mg x kg(-1) x day(-1) KRP-101 (n = 5) or vehicle (n = 5) was administered orally once a day. KRP-101 administration resulted in a significantly lower weight of overall visceral fat, which is associated with increased adiponectin and decreased leptin in serum. KRP-101 administration improved hyperglycemia and hyperinsulinemia as well as dyslipidemia in dogs fed a high-fat diet. Oral glucose tolerance test showed that KRP-101 administration improved glucose intolerance. The KRP-101 group showed a markedly lower hepatic triglyceride concentration. Lipid oxidation was increased in the liver and skeletal muscles of the KRP-101 gro...Continue Reading

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Citations

Aug 1, 2009·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Seok Joon ShinCheol Whee Park
Apr 28, 2009·Veterinary Clinical Pathology·M Judith RadinBethany J Holycross
Jan 19, 2010·Research in Veterinary Science·Y HatanoT Arai
Nov 10, 2009·Bioscience, Biotechnology, and Biochemistry·Mamoru TanidaKatsuya Nagai
Jun 29, 2017·International Journal of Medicinal Chemistry·Neelaveni ThangavelHassan A Alhazmi
Nov 3, 2020·Domestic Animal Endocrinology·D D MiceliV A Castillo
May 7, 2021·Veterinary Medicine and Science·Fausto QuintavallaRoberto Ramoni
Sep 10, 2008·Clinical Nutrition : Official Journal of the European Society of Parenteral and Enteral Nutrition·Raquel HontecillasJosep Bassaganya-Riera

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