Mice lacking triglyceride synthesis enzymes in adipose tissue are resistant to diet-induced obesity Journal Article


Authors: Chitraju, C.; Fischer, A. W.; Ambaw, Y. A.; Wang, K.; Yuan, B.; Hui, S.; Walther, T. C.; Farese, R. V. Jr
Article Title: Mice lacking triglyceride synthesis enzymes in adipose tissue are resistant to diet-induced obesity
Abstract: Triglycerides (TGs) in adipocytes provide the major stores of metabolic energy in the body. Optimal amounts of TG stores are desirable as insufficient capacity to store TG, as in lipodystrophy, or exceeding the capacity for storage, as in obesity, results in metabolic disease. We hypothesized that mice lacking TG storage in adipocytes would result in excess TG storage in cell types other than adipocytes and severe lipotoxicity accompanied by metabolic disease. To test this hypothesis, we selectively deleted both TG synthesis enzymes, DGAT1 and DGAT2, in adipocytes (ADGAT DKO mice). As expected with depleted energy stores, ADGAT DKO mice did not tolerate fasting well and, with prolonged fasting, entered torpor. However, ADGAT DKO mice were unexpectedly otherwise metabolically healthy and did not accumulate TGs ectopically or develop associated metabolic perturbations, even when fed a high-fat diet. The favorable metabolic phenotype resulted from activation of energy expenditure, in part via BAT (brown adipose tissue) activation and beiging of white adipose tissue. Thus, the ADGAT DKO mice provide a fascinating new model to study the coupling of metabolic energy storage to energy expenditure. © 2023, Chitraju et al.
Keywords: mouse; animal; metabolism; animals; mice; obesity; triacylglycerol; medicine; adipose tissue; triglycerides; fat; lipid diet; glucose metabolism; adipocyte; brown adipose tissue; adipocytes; adipose tissue, brown; lipodystrophy; diet, high-fat; triglyceride
Journal Title: eLife
Volume: 12
ISSN: 2050-084X
Publisher: eLife Sciences Publications Ltd.  
Date Published: 2023-10-02
Start Page: RP88049
Language: English
DOI: 10.7554/eLife.88049
PUBMED: 37782317
PROVIDER: scopus
PMCID: PMC10545428
DOI/URL:
Notes: Source: Scopus
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  1. Robert V Farese
    5 Farese
  2. Yohannes Abere Ambaw
    3 Ambaw