the curve analysis; LF-C: 2534±124, HF-C: 3371±186 mM*min, P
Integrated Physiology/ Obesity POSTERS inhibitory protein Bcl2. Phospho proteomic analysis and phospho-specifi c immunoblotting demonstrated an increased tyrosine phosphorylation of STAT3, a known transcriptional activator of Bcl2 expression. Expression of a dominant-interfering STAT3 mutant (STAT3-Y705A) was a potent activator of skeletal muscle macroautophagy. Together these data demonstrate that Fyn functions as a suppressor of macroautophagy through a STAT3 mediated inhibition of the Vps34/Beclin1/ATG14 complex 1. Supported by: NIH & 1723-P Macrophages Are Necessary for Exercise-Induced Enhancement of Insulin Sensitivity in Skeletal Muscle SHIN-ICHI IKEDA, YOSHIFUMI TAMURA, SAORI KAKEHI, YOSHIO FUJITANI, TAKAHISA HIROSE, RYUZO KAWAMORI, HIROTAKA WAT<strong>ADA</strong>, Tokyo, Japan Type 2 diabetes and obesity are characterized by insulin resistance in skeletal muscle. It has been well demonstrated that exercise increase insulin sensitivity in skeletal muscle. However, it remains still unclear how a single bout exercise enhance subsequent insulin sensitivity. The understanding of this mechanism would eventually contribute to further development of treatment for type 2 diabetes. Recently, it has been reported that infl ammatory M1 macrophages (MAC) are associated with development of insulin resistance and anti-infl ammatory M2 MAC have positive effect on insulin sensitivity in several insulin target organs, such as adipose tissue, liver and skeletal muscle. We, therefore, hypothesized that MAC, especially M2, are involved in the mechanisms of exercise-induced enhancement of insulin sensitivity in skeletal muscle. To test this hypothesis, we injected PBScontaining liposome (PBS) or clodronate-containing liposome (CL), a MAC suppressor, to C57BL6J mice. Then, mice were subjected to a single bout of treadmill running (20m/min, 90 min). Twenty-four hour after exercise, we measured ex-vivo insulin-stimulated 2-deoxy glucose (DG) uptake in skeletal muscle. We observed that a single bout exercise enhanced CD206 (M2 MAC marker)-positive MAC accumulation and insulin-stimulated 2-DG uptake in plantaris muscle in PBS group (Figure 1). However, CL treatment completely abolished MAC accumulation and enhanced insulin sensitivity in skeletal muscle (Figure 1). We also observed that basal AMPK phosphorylation and insulin-induced phosphorylation state of Akt and AS160 were not changed by exercise or CL treatment in plantaris muscle. From these results, we conclude that MAC is involved in enhancement of insulin sensitivity in skeletal muscle after exercise, independent of Akt and AMPK activity. & 1724-P Selective over Expression of Toll-Like Receptor 4 in Skeletal Muscle Causes Impaired Adaptation to High-Fat Feeding RYAN MCMILLAN, YARU WU, KEVIN VOELKER, JOHN KAVANAUGH, KRISTIN WAHLBERG, ANGELA ANDERSON, KIM HAYNIE, MORDECAI HARVEY, GABRIELLE FUNDARO, ELIKA SHABROKH, MADLYN FRISARD, RANDY MYNATT, MATTHEW HULVER, Blacksburg, VA, Baton Rouge, LA Our laboratory has shown that toll-like receptor 4 (TLR4) is elevated in skeletal muscle of obese humans and its activation results in a partitioning of fatty acids toward storage at the expense of oxidative pathways. To better understand this phenomenon, we developed a mouse model, on C57Bl/6 background, with selective over expression of TLR4 in skeletal muscle (mTLR4). Mice were metabolically characterized on chow and a 45% high fat (HF) diet. Skeletal muscle from mTLR4 mice displayed heightened activation of pro-infl ammatory pathways as evidenced by increased protein levels of interleukin-6 and tumor necrosis factor-alpha. On a chow diet, fasting For author disclosure information, see page 785. INTEGRATED CATEGORY PHYSIOLOGY—MUSCLE A468 palmitate oxidation was 27% lower in red skeletal muscle from mTLR4 mice compared to wild-type (WT); no differences were observed in white muscle. Following 16 weeks of HF diet, fatty acid oxidation was signifi cantly increased in WT mice (+17.8%, p
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