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April 19, 2004Proceedings of the National Academy of SciencesOpen Access

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

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Key result

Adenovirus-mediated hepatic overexpression of insig-1 or insig-2 significantly reduced plasma triglycerides (from 707 mg/dl to 369 and 183 mg/dl, respectively) and hepatic steatosis in obese Zucker diabetic fatty rats.

Why the study?

Does hepatic overexpression of insig-1 or insig-2 reduce lipogenesis in obese Zucker diabetic fatty rats?

Population

Zucker diabetic fatty (ZDF) (fa/fa) male rats and lean wild-type (+/+) ZDF-drt male rats, aged 7 or 13 weeks.

Comparison

Intravenous injection of 5x10^11 or 1x10^12 pfu… vs Intravenous injection of recombinant adenovirus…

Design

Preclinical

Follow-up

up to 3 weeks

Authors

KTKiyosumi TakaishiDaiichi Sankyo (Germany)LDLaurence DuplombInsermMWMay-Yun WangThe University of Texas Southwestern Medical Center

Discussion

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Implication

Hepatic insig-1/2 overexpression may curb steatosis in obese rats; hypothesis-generating for SREBP-targeted therapies in human metabolic disease.

Structured PICO

Does hepatic overexpression of insig-1 or insig-2 reduce lipogenesis in obese Zucker diabetic fatty rats?

P
Population
Male Zucker diabetic fatty (fa/fa) rats and lean wild-type rats, aged 7 to 13 weeks, used to study the antilipogenic effects of insig-1 and -2 overexpression.
I
Intervention
Intravenous injection of 5x10^11 or 1x10^12 pfu of recombinant adenovirus containing mouse insig-1 or insig-2 cDNA (AdCMV-insig-1 or AdCMV-insig-2).
C
Comparator
Intravenous injection of recombinant adenovirus containing beta-galactosidase cDNA (AdCMV-beta-gal).
O
Outcome
Plasma triacylglycerol levels and hepatic triacylglycerol content.surrogate

Main Result

Absolute Event Rate: 183% vs 707%

p-value: p=<0.005

Hepatic overexpression of insig-1 or insig-2 attenuates hepatic steatosis and hyperlipidemia in obese rats by reducing SREBP-1c-mediated lipogenesis.

Limitations

  • Animal model findings may not directly translate to human physiology
  • Short duration of follow-up
  • Endogenous insig-1 increase was insufficient to prevent lipogenesis naturally

Cite This Study

Takaishi et al. (2004) studied Hepatic steatosis and hyperlipidemia in obesity. AdCMV-insig-1 or AdCMV-insig-2 vs. AdCMV-beta-gal was evaluated on Plasma triacylglycerol (TG) levels at 12 days post-treatment (mg/dl) (p=<0.005). Adenovirus-mediated hepatic overexpression of insig-1 or insig-2 significantly reduced plasma triglycerides (from 707 mg/dl to 369 and 183 mg/dl, respectively) and hepatic steatosis in obese Zucker diabetic fatty rats.

synapsesocial.com/papers/6a896f70f8670bac6e334367https://doi.org/10.1073/pnas.0401715101
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Also Consider

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  1. 1Regulation of sterol regulatory element binding proteins in livers of fasted and refed mice1998 · 672 citations
  2. 2Independent regulation of sterol regulatory element-binding proteins 1 and 2 in hamster liver.1995 · 305 citations
  3. 3Enhanced de novo lipogenesis in the leptin-unresponsive pancreatic islets of prediabetic Zucker diabetic fatty rats: role in the pathogenesis of lipotoxic diabetes.1998 · 77 citations
  4. 4Cloning, Human Chromosomal Assignment, and Adipose and Hepatic Expression of the CL-6/INSIG1 Gene1997 · 61 citations
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