Chow fed UC Davis strain female Lepr fatty Zucker rats exhibit mild glucose intolerance, hypertriglyceridemia, and increased urine volume, all reduced by a Brown Norway strain chromosome 1 congenic donor region

Craig H Warden, Ahmed Bettaieb, Esther Min, Janis S. Fisler, Fawaz Haj, Judith S. Stern

Research output: Contribution to journalArticle

Abstract

Our objective is to identify genes that influence the development of any phenotypes of type 2 diabetes (T2D) or kidney disease in obese animals. We use the reproductively isolated UC Davis fatty Zucker strain rat model in which the defective chromosome 4 leptin receptor (LeprfaSte/faSte) results in fatty obesity. We previously produced a congenic strain with the distal half of chromosome 1 from the Brown Norway strain (BN) on a Zucker (ZUC) background (BN.ZUC-D1Rat183–D1Rat90). Previously published studies in males showed that the BN congenic donor region protects from some phenotypes of renal dysfunction and T2D. We now expand our studies to include females and expand phenotyping to gene expression. We performed diabetes and kidney disease phenotyping in chow-fed females of the BN.ZUC-D1Rat183-D1Rat90 congenic strain to determine the specific characteristics of the UC Davis model. Fatty LeprfaSte/faSte animals of both BN and ZUC genotype in the congenic donor region had prediabetic levels of fasting blood glucose and blood glucose 2 hours after a glucose tolerance test. We observed significant congenic strain chromosome 1 genotype effects of the BN donor region in fatty females that resulted in decreased food intake, urine volume, glucose area under the curve during glucose tolerance test, plasma triglyceride levels, and urine glucose excretion per day. In fatty females, there were significant congenic strain BN genotype effects on non-fasted plasma urea nitrogen, triglyceride, and creatinine. Congenic region genotype effects were observed by quantitative PCR of mRNA from the kidney for six genes, all located in the chromosome 1 BN donor region, with potential effects on T2D or kidney function. The results are consistent with the hypothesis that the BN genotype chromosome 1 congenic region influences traits of both type 2 diabetes and kidney function in fatty UC Davis ZUC females and that there are many positional candidate genes.

Original languageEnglish (US)
Article numberY
Pages (from-to)1DUMMY
JournalPLoS One
Volume12
Issue number12
DOIs
StatePublished - Dec 1 2017

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Zucker Rats
hypertriglyceridemia
Glucose Intolerance
Hypertriglyceridemia
Chromosomes, Human, Pair 1
Norway
Chromosomes
Rats
urine
Urine
chromosomes
Glucose
glucose
rats
Type 2 Diabetes Mellitus
Genotype
Medical problems
Kidney
noninsulin-dependent diabetes mellitus
Kidney Diseases

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Chow fed UC Davis strain female Lepr fatty Zucker rats exhibit mild glucose intolerance, hypertriglyceridemia, and increased urine volume, all reduced by a Brown Norway strain chromosome 1 congenic donor region. / Warden, Craig H; Bettaieb, Ahmed; Min, Esther; Fisler, Janis S.; Haj, Fawaz; Stern, Judith S.

In: PLoS One, Vol. 12, No. 12, Y, 01.12.2017, p. 1DUMMY.

Research output: Contribution to journalArticle

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