RGD Reference Report - Hepatic insig-1 or -2 overexpression reduces lipogenesis in obese Zucker diabetic fatty rats and in fasted/refed normal rats. - Rat Genome Database

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Hepatic insig-1 or -2 overexpression reduces lipogenesis in obese Zucker diabetic fatty rats and in fasted/refed normal rats.

Authors: Takaishi, K  Duplomb, L  Wang, MY  Li, J  Unger, RH 
Citation: Takaishi K, etal., Proc Natl Acad Sci U S A. 2004 May 4;101(18):7106-11. Epub 2004 Apr 19.
RGD ID: 2308857
Pubmed: PMID:15096598   (View Abstract at PubMed)
PMCID: PMC406473   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0401715101   (Journal Full-text)

To determine whether the antilipogenic actions of insulin-induced gene 1 (insig-1) demonstrated in cultured preadipocytes also occur in vivo, we infected Zucker diabetic fatty (ZDF) (fa/fa) rats, with recombinant adenovirus containing insig-1 or -2 cDNA. An increase of both proteins appeared in their livers. In control ZDF (fa/fa) rats infected with adenovirus containing the beta-galactosidase (beta-gal) cDNA, triacylglycerols in the liver and plasma rose steeply whereas the insig-infected rats exhibited substantial attenuation of the increase in hepatic steatosis and hyperlipidemia. Insig overexpression was associated with a striking reduction in the elevated level of nuclear sterol regulatory element-binding protein (SREBP)-1c, the activated form of the transcription factor. The mRNA of SREBP-1c lipogenic target enzymes also fell. The mRNA of endogenous insig-1, but not -2a and -2b, was higher in the fatty livers of untreated obese ZDF (fa/fa) rats compared with controls, but the elevation was not sufficient to block the approximately 3-fold increase in SREBP-1c expression and activity. In normal animals, adenovirus-induced overexpression of the insigs reduced the increase in SREBP-1c mRNA and its target enzymes caused by refeeding. The findings demonstrated that both insigs have antilipogenic action when transgenically overexpressed in livers with increased SREBP-1c-mediated lipogenesis. However, the increase in endogenous insig-1 expression associated with augmented lipogenesis may limit it, but is insufficient to prevent it.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hypertriglyceridemia severityISOInsig1 (Mus musculus)2308857; 2308857associated with ObesityRGD 
Hypertriglyceridemia severityISOInsig2 (Mus musculus)2308857; 2308857associated with ObesityRGD 
Hypertriglyceridemia severityIMP 2308857; 2308857associated with ObesityRGD 
steatotic liver disease  ISOInsig1 (Rattus norvegicus)2308857; 2308857associated with Obesity and mRNA:increased expression:liverRGD 
steatotic liver disease severityISOInsig1 (Mus musculus)2308857; 2308857associated with ObesityRGD 
steatotic liver disease severityISOInsig2 (Mus musculus)2308857; 2308857associated with ObesityRGD 
steatotic liver disease severityIMP 2308857; 2308857associated with ObesityRGD 
steatotic liver disease  IEP 2308857associated with Obesity and mRNA:increased expression:liverRGD 

Objects Annotated

Genes (Rattus norvegicus)
Insig1  (insulin induced gene 1)
Insig2  (insulin induced gene 2)

Genes (Mus musculus)
Insig1  (insulin induced gene 1)
Insig2  (insulin induced gene 2)

Genes (Homo sapiens)
INSIG1  (insulin induced gene 1)
INSIG2  (insulin induced gene 2)


Additional Information