Metabolic syndrome in mice induced by expressing a transcriptional activator in adipose tissue.
Metabolic syndrome is a combination of medical disorders that increases the risk of developing cardiovascular disease and diabetes. Constitutive overexpression of 11β-HSD1 in adipose tissue in mice leads to metabolic syndrome. In the process of generating transgenic mice overexpressing 11β-HSD1 in an inducible manner, we found a metabolic syndrome phenotype in control, transgenic mice, expressing the reverse tetracycline-transactivator (rtTA) in adipose tissue. The control mice exhibited all four sequelae of metabolic syndrome (visceral obesity, insulin resistance, dyslipidemia, and hypertension), a pro-inflammatory state and marked hepatic steatosis. Gene expression profiling of the adipose tissue, muscle and liver of these mice revealed changes in expression of genes involved in lipid metabolism, insulin resistance, and inflammation. Transient transfection of rtTA, but not tTS, into 3T3-L1 cells resulted in lipid accumulation. We conclude that expression of rtTA in adipose tissue causes metabolic syndrome in mice.
Department of Cardiovascular Diseases, Merck Research Laboratories, Rahway, NJ 07065, USA.
Liwen
L
Zhang
Yuchen
Y
Zhou
Amber Ying
AY
Zhu
Xiang-qing
XQ
Li
Steven S
SS
Mundt
Ling
L
Gao
JeanMarie
J
Lisnock
Melba
M
Hernandez
Magdalena
M
Alonso-Galicia
Martin S
MS
Springer
Edward A
EA
O'Neill
Bruce L
BL
Daugherty
Oscar
O
Puig
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism; D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001794:Blood Pressure; D033481:Chromosomes, Mammalian / Q000235:genetics / Q000378:metabolism; D053938:DNA Fragmentation; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D013752:Tetracycline / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D019076:Transgenes
D015534:Trans-Activators; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D013752:Tetracycline