eLife (Oct 2023)

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

  • Chandramohan Chitraju,
  • Alexander W Fischer,
  • Yohannes A Ambaw,
  • Kun Wang,
  • Bo Yuan,
  • Sheng Hui,
  • Tobias C Walther,
  • Robert V Farese Jr

DOI
https://doi.org/10.7554/eLife.88049
Journal volume & issue
Vol. 12

Abstract

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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.

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