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Cited by 206Lipid metabolism and biosynthesisLipid metabolism and disordersAdipose Tissue and Metabolism

The triglyceride synthesis enzymes DGAT1 and DGAT2 have distinct and overlapping functions in adipocytes

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Chitraju, Chandramohan, Walther, Tobias C., Farese, Robert V.·2019·Journal of Lipid Research
DOI 10.1194/jlr.m093112PMC PMC6547635
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Abstract

Mammals store metabolic energy as triacylglycerols (TGs) in adipose tissue. TG synthesis is catalyzed by the evolutionarily unrelated acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes DGAT1 and DGAT2, which catalyze the same reaction and account for nearly all TG synthesis. The reasons for their convergent evolution to synthesize TGs remain unclear. Mice lacking DGAT1 are viable with reduced fat stores of TGs, whereas DGAT2 KO mice die postnatally just after birth with >90% reduction of TGs, suggesting that DGAT2 is the predominant enzyme for TG storage. To better understand the functional differences between the DGATs, we studied mice fed chow or high-fat diets lacking either enzyme in adipose tissue. Unexpectedly, mice lacking DGAT2 in adipocytes have normal TG storage and glucose metabolism on regular or high-fat diets, indicating DGAT2 is not essential for fat storage. In contrast, mice lacking DGAT1 in adipocytes have normal TG storage on a chow diet but moderately decreased body fat accompanied by glucose intolerance when challenged with a high-fat diet. The latter changes were associated with the activation of ER stress pathways. We conclude that DGAT1 and DGAT2 can largely compensate for each other for TG storage but that DGAT1 uniquely has an important role in protecting the ER from the lipotoxic effects of high-fat diets.

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Authors
Chitraju, C., Walther, T. C., & Farese, R. V.
Affiliations
  • Harvard University (US)
  • Broad Institute (US)
Corresponding author
Walther, Tobias C.
ORCID
Venue
Journal of Lipid Research
Publisher
Elsevier BV
Published
2019-06
Volume
60
Issue
6
Pages
1112-1120
ISSN
0022-2275 (ISSN-L)
DOI
10.1194/jlr.m093112
PMC
PMC6547635
OpenAlex
W2932544732
Cited by
206
References
7
Citations by year
2026: 28 · 2025: 23 · 2024: 36 · 2023: 34 · 2022: 34 · 2021: 32 · 2020: 15 · 2019: 4
FWCI
9.29
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Lipid Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • American Diabetes Association (mentor-based fellowship Grant 7-12-MN-18)
  • National Institutes of Health (R01 DK101579, RO1 DK056084, R01 GM097194)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
DGAT1, DGAT2, triglyceride synthesis, adipocytes, adipose tissue, endoplasmic reticulum stress, impaired glucose tolerance, high-fat diet, lipotoxicity, convergent evolution, body fat storage
MeSH terms
Adipose Tissue, Animals, Epidermis, Mice, Inbred C57BL, Obesity, Triglycerides, Immunoblotting, Adipocytes, Diacylglycerol O-Acyltransferase, Mice, Diet, High-Fat, Endoplasmic Reticulum Stress

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