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This study tested the hypothesis that the reduction in <jats:styled-content style=\"fixed-case\">WAT<\/jats:styled-content> mass in chronic alcohol\u2010fed mice is associated with a decreased protein synthesis specifically related to impaired function of mammalian target of rapamycin (<jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult male mice were provided an alcohol\u2010containing liquid diet for 24\u00a0weeks or an isonitrogenous isocaloric control diet. In vivo protein synthesis was determined at this time and thereafter epididymal <jats:styled-content style=\"fixed-case\">WAT<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">eWAT<\/jats:styled-content>) was excised for analysis of signal transduction pathways central to controling protein synthesis and degradation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>While chronic alcohol feeding decreased whole\u2010body and <jats:styled-content style=\"fixed-case\">eWAT<\/jats:styled-content> mass, this was associated with a discordant increase in protein synthesis in <jats:styled-content style=\"fixed-case\">eWAT<\/jats:styled-content>. This increase was not associated with a change in <jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content>, 4E\u2010<jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content>1, Akt, or <jats:styled-content style=\"fixed-case\">PRAS<\/jats:styled-content>40 phosphorylation. Instead, a selective increase in phosphorylation of S6K1 and its downstream substrates, S6 and <jats:styled-content style=\"fixed-case\">eIF<\/jats:styled-content>4B was detected in alcohol\u2010fed mice. Alcohol also increased <jats:styled-content style=\"fixed-case\">eEF<\/jats:styled-content>2K phosphorylation and decreased <jats:styled-content style=\"fixed-case\">eEF<\/jats:styled-content>2 phosphorylation consistent with increased translation elongation. Alcohol increased Atg12\u20105, <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3B\u2010I and \u2010<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">ULK<\/jats:styled-content>1 S555 phosphorylation, suggesting increased autophagy, while markers of apoptosis (cleaved caspase\u20103 and \u20109, and <jats:styled-content style=\"fixed-case\">PARP<\/jats:styled-content>) were unchanged. Lipolytic enzymes (<jats:styled-content style=\"fixed-case\">ATGL<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">HSL<\/jats:styled-content> phosphorylation) were increased and lipogenic regulators (<jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b3 and C\/<jats:styled-content style=\"fixed-case\">EBP<\/jats:styled-content>\u03b1) were decreased in <jats:styled-content style=\"fixed-case\">eWAT<\/jats:styled-content> by alcohol. Although alcohol increased <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106, and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>, no change in key components of the <jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3 inflammasome (<jats:styled-content style=\"fixed-case\">NLRP<\/jats:styled-content>3, <jats:styled-content style=\"fixed-case\">ACS<\/jats:styled-content>, and cleaved caspase\u20101) was detected suggesting alcohol did not increase pyroptosis. Plasma insulin did not differ between groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results demonstrate that the alcohol\u2010induced decrease in whole\u2010body fat mass resulted in part from activation of autophagy in <jats:styled-content style=\"fixed-case\">eWAT<\/jats:styled-content> as protein synthesis was increased and mediated by the specific increase in the activity of S6K1.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13159","type":"journal-article","created":{"date-parts":[[2016,7,27]],"date-time":"2016-07-27T12:34:37Z","timestamp":1469622877000},"page":"1832-1845","source":"Crossref","is-referenced-by-count":23,"title":["Decreased Whole\u2010Body Fat Mass Produced by Chronic Alcohol Consumption is Associated with Activation of S6K1\u2010Mediated Protein Synthesis and Increased Autophagy in Epididymal White Adipose Tissue"],"prefix":"10.1111","volume":"40","author":[{"given":"Kristen T.","family":"Crowell","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Physiology Penn State College Medicine Hershey Pennsylvania"},{"name":"Department of Surgery Penn State College Medicine Hershey Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"Steiner","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology Penn State College Medicine Hershey Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine S.","family":"Coleman","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology Penn State College Medicine Hershey Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles H.","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology Penn State College Medicine Hershey Pennsylvania"},{"name":"Department of Surgery Penn State College Medicine Hershey Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,7,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3350417"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2008.645"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M021485"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1256804"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1602"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2007.04.002"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2015.06.002"},{"key":"e_1_2_7_9_1","doi-asserted-by":"crossref","first-page":"22770","DOI":"10.1016\/S0021-9258(18)54634-2","article-title":"Mitogen\u2010activated 70K S6 kinase. 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