DGAT1 Induced Lipid Turnover Figure 6. DGAT1 overexpression results in bigger lipid droplets in HFD-fed rats. (A) Electron microscopy revealed an increase in lipid droplet diameter in DGAT1 overexpressing TA muscle of HFD-fed rats. (B) Western blot analysis of OXPAT in rat TA muscle. Data are expressed as mean 6 SEM (n = 10–12). doi:10.1371/journal.pone.0014503.g006 of DGAT1. Interestingly, electron microscopy revealed that overexpression of DGAT1 in animals receiving the HFD mainly resulted in an increased size of the lipid droplets, rather than an increased number. The increase in lipid droplet size in the HFD- DGAT1 overexpressing leg, compared with the empty vector control leg, was associated with an increase in the content of the lipid droplet coating proteins OXPAT and ADRP, which are thought to play a role in lipid synthesis and breakdown [28]. In CHO cells it was shown that ADRP is ubiquitinated and degraded by proteolysis when TAG levels decreased whereas inhibition of ADRP proteolysis led to a 2.8 fold increase in TAG levels [29]. Furthermore, improvement of human skeletal muscle insulin Figure 7. The turnover of DAG and TAG is increased in the DGAT1 overexpressing TA muscle. (A) Western blotting of ATGL, (B) CGI58 (C) and ADRP in rat TA muscle. Data are expressed as mean 6 SEM (n = 10–12). # P,0.05 HFD-DGAT1 vs. HFD-control. doi:10.1371/journal.pone.0014503.g007 PLoS ONE | www.plosone.org 8 January 2011 | Volume 6 | Issue 1 | e14503