title: Mechanisms of Comorbidities Associated With the Metabolic Syndrome: Insights from theJCR:LA-cpCorpulent Rat Strain.
abstract: Obesity and its metabolic complications have emerged as the epidemic of the new millennia. The use of obese rodent models continues to be a productive component of efforts to understand the concomitant metabolic complications of this disease. In 1978, theJCR:LA-cprat model was developed with an autosomal recessive corpulent (cp) trait resulting from a premature stop codon in the extracellular domain of the leptin receptor. Rats that are heterozygous for thecptrait are lean-prone, while those that are homozygous (cp/cp) spontaneously display the pathophysiology of obesity as well as a metabolic syndrome (MetS)-like phenotype. Over the years, there have been formidable scientific contributions that have originated from this rat model, much of which has been reviewed extensively up to 2008. The premise of these earlier studies focused on characterizing the pathophysiology of MetS-like phenotype that was spontaneously apparent in this model. The purpose of this review is to highlight areas of recent advancement made possible by this model including; emerging appreciation of the "thrifty gene" hypothesis in the context of obesity, the concept of how chronic inflammation may drive obesogenesis, the impact of acute forms of inflammation to the brain and periphery during chronic obesity, the role of dysfunctional insulin metabolism on lipid metabolism and vascular damage, and the mechanistic basis for altered vascular function as well as novel parallels between the human condition and the femaleJCR:LA-cprat as a model for polycystic ovary disease (PCOS).
authors: Metabolic and Cardiovascular Diseases Laboratory, Division of Human Nutrition, Alberta Diabetes and Mazakowski Heart Institutes, University of Alberta , Edmonton, AB , Canada.
authors: Abdoulaye
authors: A
authors: Diane
authors: Department of Sociology, University of Alberta , Edmonton, AB , Canada.
authors: W David
authors: WD
authors: Pierce
authors: Metabolic and Cardiovascular Diseases Laboratory, Division of Human Nutrition, Alberta Diabetes and Mazakowski Heart Institutes, University of Alberta , Edmonton, AB , Canada.
authors: Sandra E
authors: SE
authors: Kelly
authors: Metabolic and Cardiovascular Diseases Laboratory, Division of Human Nutrition, Alberta Diabetes and Mazakowski Heart Institutes, University of Alberta , Edmonton, AB , Canada.
authors: Sharon
authors: S
authors: Sokolik
authors: Metabolic and Cardiovascular Diseases Laboratory, Division of Human Nutrition, Alberta Diabetes and Mazakowski Heart Institutes, University of Alberta , Edmonton, AB , Canada.
authors: Faye
authors: F
authors: Borthwick
authors: Metabolic and Cardiovascular Diseases Laboratory, Division of Human Nutrition, Alberta Diabetes and Mazakowski Heart Institutes, University of Alberta , Edmonton, AB , Canada.
authors: Miriam
authors: M
authors: Jacome-Sosa
authors: Metabolic and Cardiovascular Diseases Laboratory, Division of Human Nutrition, Alberta Diabetes and Mazakowski Heart Institutes, University of Alberta , Edmonton, AB , Canada.
authors: Rabban
authors: R
authors: Mangat
authors: Universidad Complutense de Madrid , Madrid , Spain.
authors: Jesus Miguel
authors: JM
authors: Pradillo
authors: Faculty of Biology, Medicine and Health, University of Manchester , Manchester , UK.
authors: Stuart McRae
authors: SM
authors: Allan
authors: Department of Agricultural Food and Nutritional Science, University of Alberta , Edmonton, AB , Canada.
authors: Megan R
authors: MR
authors: Ruth
authors: Department of Agricultural Food and Nutritional Science, University of Alberta , Edmonton, AB , Canada.
authors: Catherine J
authors: CJ
authors: Field
authors: New York Medical College , New York, NY , USA.
authors: Rebecca
authors: R
authors: Hutcheson
authors: New York Medical College , New York, NY , USA.
authors: Petra
authors: P
authors: Rocic
authors: Metabolic and Cardiovascular Diseases Laboratory, Division of Human Nutrition, Alberta Diabetes and Mazakowski Heart Institutes, University of Alberta , Edmonton, AB , Canada.
authors: James C
authors: JC
authors: Russell
authors: Metabolic and Cardiovascular Diseases Laboratory, Division of Human Nutrition, Alberta Diabetes and Mazakowski Heart Institutes, University of Alberta , Edmonton, AB , Canada.
authors: Donna F
authors: DF
authors: Vine
authors: Metabolic and Cardiovascular Diseases Laboratory, Division of Human Nutrition, Alberta Diabetes and Mazakowski Heart Institutes, University of Alberta , Edmonton, AB , Canada.
authors: Spencer D
authors: SD
authors: Proctor
keywords: JCR rat; cardiovascular diseases; immune function; inflammation; metabolic syndrome; obesity; pcos; thrifty genotype