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Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver.

Publication ,  Journal Article
Monetti, M; Levin, MC; Watt, MJ; Sajan, MP; Marmor, S; Hubbard, BK; Stevens, RD; Bain, JR; Newgard, CB; Farese, RV; Hevener, AL
Published in: Cell Metab
July 2007

Hepatic steatosis, the accumulation of lipids in the liver, is widely believed to result in insulin resistance. To test the causal relationship between hepatic steatosis and insulin resistance, we generated mice that overexpress acyl-CoA:diacylglycerol acyltransferase 2 (DGAT2), which catalyzes the final step of triacylglycerol (TG) biosynthesis, in the liver (Liv-DGAT2 mice). Liv-DGAT2 mice developed hepatic steatosis, with increased amounts of TG, diacylglycerol, ceramides, and unsaturated long-chain fatty acyl-CoAs in the liver. However, they had no abnormalities in plasma glucose and insulin levels, glucose and insulin tolerance, rates of glucose infusion and hepatic glucose production during hyperinsulinemic-euglycemic clamp studies, or activities of insulin-stimulated signaling proteins in the liver. DGAT1 overexpression in the liver also failed to induce glucose or insulin intolerance. Our results indicate that DGAT-mediated lipid accumulation in the liver is insufficient to cause insulin resistance and show that hepatic steatosis can occur independently of insulin resistance.

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Published In

Cell Metab

DOI

ISSN

1550-4131

Publication Date

July 2007

Volume

6

Issue

1

Start / End Page

69 / 78

Location

United States

Related Subject Headings

  • Triglycerides
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Macrophages, Peritoneal
  • Liver
  • Insulin Resistance
  • Insulin
  • Hyperinsulinism
 

Citation

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Monetti, M., Levin, M. C., Watt, M. J., Sajan, M. P., Marmor, S., Hubbard, B. K., … Hevener, A. L. (2007). Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver. Cell Metab, 6(1), 69–78. https://doi.org/10.1016/j.cmet.2007.05.005
Monetti, Mara, Malin C. Levin, Matthew J. Watt, Mini P. Sajan, Stephen Marmor, Brian K. Hubbard, Robert D. Stevens, et al. “Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver.Cell Metab 6, no. 1 (July 2007): 69–78. https://doi.org/10.1016/j.cmet.2007.05.005.
Monetti M, Levin MC, Watt MJ, Sajan MP, Marmor S, Hubbard BK, et al. Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver. Cell Metab. 2007 Jul;6(1):69–78.
Monetti, Mara, et al. “Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver.Cell Metab, vol. 6, no. 1, July 2007, pp. 69–78. Pubmed, doi:10.1016/j.cmet.2007.05.005.
Monetti M, Levin MC, Watt MJ, Sajan MP, Marmor S, Hubbard BK, Stevens RD, Bain JR, Newgard CB, Farese RV, Hevener AL. Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver. Cell Metab. 2007 Jul;6(1):69–78.
Journal cover image

Published In

Cell Metab

DOI

ISSN

1550-4131

Publication Date

July 2007

Volume

6

Issue

1

Start / End Page

69 / 78

Location

United States

Related Subject Headings

  • Triglycerides
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Macrophages, Peritoneal
  • Liver
  • Insulin Resistance
  • Insulin
  • Hyperinsulinism