DGAT1 Induced Lipid Turnover Figure 5. DGAT1 overexpression is associated with an increased mitochondrial function and biogenesis in HFD-fed rats. (A) Western blot analysis of PGC1a (B) OXPHOS complexes and (C) UCP3 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.g005 expression (p = 0.90, CHOW-DGAT1 vs. CHOW-control leg, figure 7C). Discussion Elevated IMCL levels have been associated with the development of insulin resistance. Yet, insulin-sensitive, endurance trained athletes are also characterized by high IMCL levels. It has therefore been suggested that not IMCL, but rather intermediates of intramuscular triglyceride metabolism, such as DAG are causally related to insulin resistance. DGAT1 converts DAG into TAG in skeletal muscle, and increased DGAT1 activity has been suggested to explain the athlete’s paradox [14,16,17]. In this study we show that DGAT1 overexpression in muscle of adult male Wistar rats indeed augments the storage of IMCL, but remarkably also results in increased skeletal muscle DAG content, even though a marked improvement in insulin sensitivity was observed. Our results suggest that increased intramuscular DAG and TAG turnover may underlie the beneficial effects on muscle insulin sensitivity. In our study, short-term overexpression of DGAT1 resulted in a significantly higher intramyocellular lipid content both after CHOW and HFD, as expected based upon the primary function PLoS ONE | www.plosone.org 6 January 2011 | Volume 6 | Issue 1 | e14503