title: Characterization of the ZDSD Rat: A Translational Model for the Study of Metabolic Syndrome and Type 2 Diabetes.
abstract: Metabolic syndrome and T2D produce significant health and economic issues. Many available animal models have monogenic leptin pathway mutations that are absent in the human population. Development of the ZDSD rat model was undertaken to produce a model that expresses polygenic obesity and diabetes with an intact leptin pathway. A lean ZDF rat with the propensity for beta-cell failure was crossed with a polygenetically obese Crl:CD (SD) rat. Offspring were selectively inbred for obesity and diabetes for >30 generations. In the current study, ZDSD rats were followed for 6 months; routine clinical metabolic endpoints were included throughout the study. In the prediabetic metabolic syndrome phase, ZDSD rats exhibited obesity with increased body fat, hyperglycemia, insulin resistance, dyslipidemia, glucose intolerance, and elevated HbA1c. As disease progressed to overt diabetes, ZDSD rats demonstrated elevated glucose levels, abnormal oral glucose tolerance, increases in HbA1c levels, reductions in body weight, increased insulin resistance with decreasing insulin levels, and dyslipidemia. The ZDSD rat develops prediabetic metabolic syndrome and T2D in a manner that mirrors the development of metabolic syndrome and T2D in humans. ZDSD rats will provide a novel, translational animal model for the study of human metabolic diseases and for the development of new therapies.
authors.affiliation: PreClinOmics, Inc., 7918 Zionsville Road, Indianapolis, IN 46268, USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Peterson
authors.affiliation: PreClinOmics, Inc., 7918 Zionsville Road, Indianapolis, IN 46268, USA.
authors.forename: Charles V
authors.identifier: 0000-0002-9265-6992
authors.initials: CV
authors.lastname: Jackson
authors.affiliation: PreClinOmics, Inc., 7918 Zionsville Road, Indianapolis, IN 46268, USA.
authors.forename: Karen
authors.identifier: 0000-0003-4748-5570
authors.initials: K
authors.lastname: Zimmerman
authors.affiliation: Janssen Research & Development, A Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium.
authors.forename: Willem
authors.initials: W
authors.lastname: de Winter
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA 19477, USA.
authors.forename: Norman
authors.initials: N
authors.lastname: Huebert
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA 19477, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Hansen
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D018149:Glucose Intolerance / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000378:metabolism*; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000503:physiopathology; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin