Differentielle hepatische Genexpression in einem Mausmodell mit polygener Adipositas, Insulinresistenz und Hyperglykämie

New Zealand Obese (NZO) mice exhibit a polygenic syndrome of morbid obesity and insulin resistance, that resembles the human metabolic syndrome. In order to define its biochemical basis, the differential expression of genes involved in hepatic glucose and lipid metabolism was studied. An outcross model of obese NZO mice with the lean SJL strain was established. NZOxF1 (SJLxNZO) backcross mice were generated in order to obtain a population with heterogeneous metabolism but comparable genetic background. Groups of normal (normoglycemic/normoinsulinemic), insulin-resistant (normoglycemic/hyperinsulinemic) and diabetic (hyperglycemic/hypoinsulinemic) mice were identified. Parental SJL-mice were used as control. Mice received high fat or standard diet. At 22 weeks, mice were killed and RNA isolated from liver. Differential gene expression of genes chosen for various reasons (array-analysis, literature search and gene localization near a diabetogenic locus) was assessed by Northern and Dot blotting. The data indicate that 1) insulin resistance is associated with increased expression of enzymes involved in lipogenesis and in fatty acid oxidation, whereas 2) gluconeogenic enzymes are not repressed, 3) high fat diet enhanced lipid synthesis, 4) several enzymes display sex dimorphism (SCPx, PLTP, Hsd3b5). The gene expression in insulin resistance reflects a dissociation of the effects of insulin on genes involved in glucose and lipid metabolism in liver: insulin-resistant hepatic glucose production causes hyperinsulinemia, which then enhances lipogenesis and thus further aggravates insulin resistance in a circulus vitiosus. Analysis of differential expression of the adipokines leptin and resistin in adipocytes displays a correlation between BMI and leptin-mRNA and no differences in resistin gene expression.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2005

Author dc:creator

• Linnartz, Katharina

Contributors dc:contributor

• Becker, Walter

• info:eu-repo/classification/ddc/610
• Medizin
• Insulinresistenz
• Diabetes mellitus
• NZO-Maus
• hepatische Genexpression

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-114799%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A52586