{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T08:09:59Z","timestamp":1773994199680,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2017,6,27]],"date-time":"2017-06-27T00:00:00Z","timestamp":1498521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK088940"],"award-info":[{"award-number":["DK088940"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5T32AR48523\u20108"],"award-info":[{"award-number":["5T32AR48523\u20108"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1DK078184"],"award-info":[{"award-number":["RO1DK078184"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P40OD021331"],"award-info":[{"award-number":["P40OD021331"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["14POST20110034"],"award-info":[{"award-number":["14POST20110034"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,7,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Low intrinsic aerobic capacity is associated with increased all\u2010cause and liver\u2010related mortality in humans.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Low intrinsic aerobic capacity in the low capacity runner (LCR) rat increases susceptibility to acute and chronic high\u2010fat\/high\u2010sucrose diet\u2010induced steatosis, without observed increases in liver inflammation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Addition of excess cholesterol to a high\u2010fat\/high\u2010sucrose diet produced greater steatosis in LCR and high capacity runner (HCR) rats. However, the LCR rat demonstrated greater susceptibility to increased liver inflammatory and apoptotic markers compared to the HCR rat.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The progressive non\u2010alcoholic fatty liver disease observed in the LCR rats following western diet feeding was associated with further declines in liver fatty acid oxidation and mitochondrial respiratory capacity compared to HCR rats.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Low aerobic capacity increases risk for non\u2010alcoholic fatty liver disease and liver\u2010related disease mortality, but mechanisms mediating these effects remain unknown. We recently reported that rats bred for low aerobic capacity (low capacity runner; LCR) displayed susceptibility to high fat diet\u2010induced steatosis in association with reduced hepatic mitochondrial fatty acid oxidation (FAO) and respiratory capacity compared to high aerobic capacity (high capacity runner; HCR) rats. Here we tested the impact of aerobic capacity on susceptibility for progressive liver disease following a 16\u2010week \u2018western diet\u2019 (WD) high in fat (45%\u00a0kcal), cholesterol (1%\u00a0w\/w) and sucrose (15%\u00a0kcal). Unlike previously with a diet high in fat and sucrose alone, the inclusion of cholesterol in the WD induced hepatomegaly and steatosis in both HCR and LCR rats, while producing greater cholesterol ester accumulation in LCR compared to HCR rats. Importantly, WD\u2010fed low\u2010fitness LCR rats displayed greater inflammatory cell infiltration, serum alanine transaminase, expression of hepatic inflammatory markers (F4\/80, MCP\u20101, TLR4, TLR2 and IL\u20101\u03b2) and effector caspase (caspase 3 and 7) activation compared to HCR rats. Further, LCR rats had greater WD\u2010induced decreases in complete FAO and mitochondrial respiratory capacity. Intrinsic aerobic capacity had no impact on WD\u2010induced hepatic steatosis; however, rats bred for low aerobic capacity developed greater hepatic inflammation, which was associated with reduced hepatic mitochondrial FAO and respiratory capacity and increased accumulation of cholesterol esters. These results confirm epidemiological reports that aerobic capacity impacts progression of liver disease and suggest that these effects are mediated through alterations in hepatic mitochondrial function.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp274281","type":"journal-article","created":{"date-parts":[[2017,5,15]],"date-time":"2017-05-15T12:24:45Z","timestamp":1494851085000},"page":"4909-4926","source":"Crossref","is-referenced-by-count":33,"title":["Aerobic capacity mediates susceptibility for the transition from steatosis to steatohepatitis"],"prefix":"10.1113","volume":"595","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7046-3623","authenticated-orcid":false,"given":"E. Matthew","family":"Morris","sequence":"first","affiliation":[{"name":"Department of Molecular &amp; Integrative Physiology University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin S.","family":"McCoin","sequence":"additional","affiliation":[{"name":"Department of Molecular &amp; Integrative Physiology University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie A.","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Molecular &amp; Integrative Physiology University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle L.","family":"Gastecki","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Exercise Physiology University of Missouri  Columbia MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren G.","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of Michigan  Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven L.","family":"Britton","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of Michigan  Ann Arbor MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin A.","family":"Fletcher","sequence":"additional","affiliation":[{"name":"Advanced Imaging Research Service University of Texas Southwestern  Dallas TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiarong","family":"Fu","sequence":"additional","affiliation":[{"name":"Advanced Imaging Research Service University of Texas Southwestern  Dallas TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen\u2010Xing","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Therapeutics University of Kansas Medical Center  Kansas City KS USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawn C.","family":"Burgess","sequence":"additional","affiliation":[{"name":"Advanced Imaging Research Service University of Texas Southwestern  Dallas TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. Scott","family":"Rector","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Exercise Physiology University of Missouri  Columbia MO USA"},{"name":"Harry S. Truman Memorial Veterans Hospital\u2010Research Service  Columbia MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7920-7466","authenticated-orcid":false,"given":"John P.","family":"Thyfault","sequence":"additional","affiliation":[{"name":"Department of Molecular &amp; Integrative Physiology University of Kansas Medical Center  Kansas City KS USA"},{"name":"Kansas City VA Medical Center\u2010Research Service  Kansas City MO USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,6,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.05.015"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2016.04.005"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26226"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.23766"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2007.06.012"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.03.019"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.2.554"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-302789"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2004.10.001"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2011.12.008"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202065"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)39680-2"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.07.024"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00555.2013"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.12.8075"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c120020"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.151977"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.2001.5.1.45"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP272235"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.07.018"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70506-8"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.04.004"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2010.02.010"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00093.2014"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00179.2013"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00169.2012"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00178.2016"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50132"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011858"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00500.2006"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2010.03.013"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2016.40.5.376"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00428.2007"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.11.030"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077588"},{"key":"e_1_2_6_37_1","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1093\/jn\/110.2.248","article-title":"Influence of dietary cholesterol on mitochondrial function in the rat","volume":"110","author":"Rogers KS","year":"1980","journal-title":"J Nutr"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.302.1.232"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI82204"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M023382"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(69)13005-0"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.169060"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00401.2014"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1108177"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FJP274281","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP274281","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T23:51:21Z","timestamp":1696204281000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP274281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,27]]},"references-count":43,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2017,7,15]]}},"alternative-id":["10.1113\/JP274281"],"URL":"https:\/\/doi.org\/10.1113\/jp274281","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,27]]}}}