Details

Autor(en) / Beteiligte

• Osswald, Christina
• Baumgarten, Katharina
• Stumpel, Frank
• Gorboulev, Valentin
• Akimjanova, Marina
• Knobeloch, Klaus-Peter
• Horak, Ivan
• Kluge, Reinhart
• Joost, Hans-Georg
• Koepsell, Hermann

Titel

Mice without the Regulator Gene Rsc1A1 Exhibit Increased Na super(+)-D-Glucose Cotransport in Small Intestine and Develop Obesity

Ist Teil von

• Molecular and cellular biology, 2005-01, Vol.25 (1), p.78-87

Erscheinungsjahr

2005

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• The product of the intronless single copy gene RSC1A1, named RS1, is an intracellular 617-amino-acid protein that is involved in the regulation of the Na super(+)-D-glucose cotransporter SGLT1. We generated and characterized RS1 knockout (RS1 super(-) super(/) super(-)) mice. In the small intestines of RS1 super(-) super(/) super(- ) mice, the SGLT1 protein was up-regulated sevenfold compared to that of wild- type mice but was not changed in the kidneys. The up-regulation of SGLT1 was posttranscriptional. Small intestinal D-glucose uptake measured in jointly perfused small bowel and liver was increased twofold compared to that of the wild-type, with increased peak concentrations of D-glucose in the portal vein. At birth, the weights of RS1 super(-) super(/) super(-) and wild-type mice were similar. At the age of 3 months, male RS1 super(-) super(/) super(-) mice had 5% higher weights and 15% higher food intakes, whereas their energy expenditures and serum leptin concentrations were similar to those of wild-type mice. At the age of 5 months, male and female RS1 super(-) super(/) super(-) mice were obese, with 30% increased body weight, 80% increased total fat, and 30% increased serum cholesterol. At this age, serum leptin was increased, whereas food intake was the same as for wild- type mice. The data suggest that the removal of RS1 leads to leptin-independent up-regulation of food intake, which causes obesity.