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Hepatic insulin signaling is required for obesity-dependent expression of SREBP-1c mRNA but not for feeding-dependent expression.

Publication ,  Journal Article
Haas, JT; Miao, J; Chanda, D; Wang, Y; Zhao, E; Haas, ME; Hirschey, M; Vaitheesvaran, B; Farese, RV; Kurland, IJ; Graham, M; Crooke, R ...
Published in: Cell Metab
June 6, 2012

Dissecting the role of insulin in the complex regulation of triglyceride metabolism is necessary for understanding dyslipidemia and steatosis. Liver insulin receptor knockout (LIRKO) mice show that in the physiological context of feeding, hepatic insulin signaling is not required for the induction of mTORC1, an upstream activator of the lipogenic regulator, SREBP-1c. Feeding induces SREBP-1c mRNA in LIRKO livers, though not to the extent observed in controls. A high fructose diet also partially induces SREBP-1c and lipogenic gene expression in LIRKO livers. Insulin signaling becomes more important in the pathological context of obesity, as knockdown of the insulin receptor in ob/ob mice, a model of Type 2 diabetes, using antisense oligonucleotides, abolishes the induction of SREBP-1c and its targets by obesity and ameliorates steatosis. Thus, insulin-independent signaling pathways can partially compensate for insulin in the induction of SREBP-1c by feeding but the further induction by obesity/Type 2 diabetes is entirely dependent upon insulin.

Duke Scholars

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Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

June 6, 2012

Volume

15

Issue

6

Start / End Page

873 / 884

Location

United States

Related Subject Headings

  • Triglycerides
  • Sterol Regulatory Element Binding Protein 1
  • Signal Transduction
  • Receptor, Insulin
  • RNA Interference
  • Obesity
  • Mice, Transgenic
  • Mice, Obese
  • Mice, Inbred C57BL
  • Mice
 

Citation

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Haas, J. T., Miao, J., Chanda, D., Wang, Y., Zhao, E., Haas, M. E., … Biddinger, S. B. (2012). Hepatic insulin signaling is required for obesity-dependent expression of SREBP-1c mRNA but not for feeding-dependent expression. Cell Metab, 15(6), 873–884. https://doi.org/10.1016/j.cmet.2012.05.002
Haas, Joel T., Ji Miao, Dipanjan Chanda, Yanning Wang, Enpeng Zhao, Mary E. Haas, Matthew Hirschey, et al. “Hepatic insulin signaling is required for obesity-dependent expression of SREBP-1c mRNA but not for feeding-dependent expression.Cell Metab 15, no. 6 (June 6, 2012): 873–84. https://doi.org/10.1016/j.cmet.2012.05.002.
Haas JT, Miao J, Chanda D, Wang Y, Zhao E, Haas ME, et al. Hepatic insulin signaling is required for obesity-dependent expression of SREBP-1c mRNA but not for feeding-dependent expression. Cell Metab. 2012 Jun 6;15(6):873–84.
Haas, Joel T., et al. “Hepatic insulin signaling is required for obesity-dependent expression of SREBP-1c mRNA but not for feeding-dependent expression.Cell Metab, vol. 15, no. 6, June 2012, pp. 873–84. Pubmed, doi:10.1016/j.cmet.2012.05.002.
Haas JT, Miao J, Chanda D, Wang Y, Zhao E, Haas ME, Hirschey M, Vaitheesvaran B, Farese RV, Kurland IJ, Graham M, Crooke R, Foufelle F, Biddinger SB. Hepatic insulin signaling is required for obesity-dependent expression of SREBP-1c mRNA but not for feeding-dependent expression. Cell Metab. 2012 Jun 6;15(6):873–884.
Journal cover image

Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

June 6, 2012

Volume

15

Issue

6

Start / End Page

873 / 884

Location

United States

Related Subject Headings

  • Triglycerides
  • Sterol Regulatory Element Binding Protein 1
  • Signal Transduction
  • Receptor, Insulin
  • RNA Interference
  • Obesity
  • Mice, Transgenic
  • Mice, Obese
  • Mice, Inbred C57BL
  • Mice