Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat

Steven J. Smith, Sylvaine Cases, Dalan R. Jensen, Hubert C. Chen, Eric Sande, Bryan Tow, David A. Sanan, Jacob Raber, Robert H. Eckel, Robert V. Farese

Research output: Contribution to journalArticle

650 Citations (Scopus)

Abstract

Triglycerides (or triacylglycerols) represent the major form of stored energy in eukaryotes. Triglyceride synthesis has been assumed to occur primarily through acyl CoA:diacylglycerol transferase (Dgat), a microsomal enzyme that catalyses the final and only committed step in the glycerol phosphate path- way. Therefore, Dgat has been considered necessary for adipose tissue formation and essential for survival. Here we show that Dgat- deficient (Dgat(-/-)) mice are viable and can still synthesize triglycerides. Moreover, these mice are lean and resistant to diet-induced obesity. The obesity resistance involves increased energy expenditure and increased activity. Dgat deficiency also alters triglyceride metabolism in other tissues, including the mammary gland, where lactation is defective in Dgat(- /-) females. Our findings indicate that multiple mechanisms exist for triglyceride synthesis and suggest that the selective inhibition of Dgat- mediated triglyceride synthesis may be useful for treating obesity.

Original languageEnglish (US)
Pages (from-to)87-90
Number of pages4
JournalNature Genetics
Volume25
Issue number1
DOIs
StatePublished - May 2000
Externally publishedYes

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Triglycerides
Obesity
Coenzyme A-Transferases
Acyl Coenzyme A
Diglycerides
Human Mammary Glands
Eukaryota
Lactation
Glycerol
Energy Metabolism
Adipose Tissue
Phosphates
Diet
Enzymes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Smith, S. J., Cases, S., Jensen, D. R., Chen, H. C., Sande, E., Tow, B., ... Farese, R. V. (2000). Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nature Genetics, 25(1), 87-90. https://doi.org/10.1038/75651

Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. / Smith, Steven J.; Cases, Sylvaine; Jensen, Dalan R.; Chen, Hubert C.; Sande, Eric; Tow, Bryan; Sanan, David A.; Raber, Jacob; Eckel, Robert H.; Farese, Robert V.

In: Nature Genetics, Vol. 25, No. 1, 05.2000, p. 87-90.

Research output: Contribution to journalArticle

Smith, SJ, Cases, S, Jensen, DR, Chen, HC, Sande, E, Tow, B, Sanan, DA, Raber, J, Eckel, RH & Farese, RV 2000, 'Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat', Nature Genetics, vol. 25, no. 1, pp. 87-90. https://doi.org/10.1038/75651
Smith, Steven J. ; Cases, Sylvaine ; Jensen, Dalan R. ; Chen, Hubert C. ; Sande, Eric ; Tow, Bryan ; Sanan, David A. ; Raber, Jacob ; Eckel, Robert H. ; Farese, Robert V. / Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. In: Nature Genetics. 2000 ; Vol. 25, No. 1. pp. 87-90.
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