Mice without the regulator gene Rsc1A1 exhibit increased Na+-D-glucose cotransport in small intestine and develop obesity.
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(+)-d-glucose cotransporter SGLT1. We generated and characterized RS1 knockout (RS1(-/-) mice. In the small intestines of RS1(-/-) 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(-/-) and wild-type mice were similar. At the age of 3 months, male RS1(-/-) 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(-/-) 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.
Osswald
Christina
C
Institute of Anatomy and Cell Biology, Bavarian Julius-Maximilians-University, Koellikerstrasse 6, 97070 Würzburg, Germany.
Baumgarten
Katharina
K
Stümpel
Frank
F
Gorboulev
Valentin
V
Akimjanova
Marina
M
Knobeloch
Klaus-Peter
KP
Horak
Ivan
I
Kluge
Reinhart
R
Joost
Hans-Georg
HG
Koepsell
Hermann
H
D000818:Animals; D001692:Biological Transport; D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D002784:Cholesterol / Q000097:blood; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051273:Glucose Transporter Type 2; D007328:Insulin / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D007438:Introns; D020738:Leptin / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology*; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012323:RNA Processing, Post-Transcriptional; D012737:Sex Factors; D012964:Sodium / Q000378:metabolism*; D051269:Sodium-Glucose Transporter 1; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
D051273:Glucose Transporter Type 2; D007328:Insulin; D020738:Leptin; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; C101014:RSC1A1 protein, human; C495675:Slc5a1 protein, mouse; D051269:Sodium-Glucose Transporter 1; D002784:Cholesterol; D012964:Sodium; D005947:Glucose