{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T22:35:57Z","timestamp":1772836557633,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["aspenjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Parenter Enteral Nutr"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Skeletal muscle wasting is a determinant of physical disability in survivors of critical illness. Intramuscular bioenergetic failure, altered substrate metabolim, and inflammation are likely underpinning mechanisms. We examined the effect of pioglitazone, a peroxisome proliferator\u2013activated receptor \u03b3 agonist, on muscle\u2010related outcomes in adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included randomized controlled trials in which pioglitazone was administered (no dose\/dosage restrictions) and muscle\u2010related outcomes were reported. We searched MEDLINE, CENTRAL, EMBASE, CINAHL, and trial registries. Risk of bias was assessed using RoB 2. Primary outcomes were physical function and symptoms, muscle mass and function, or body composition and muscular compositional change. Secondary outcomes included muscle insulin sensitivity, mitochondrial effects, and intramuscular inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fourteen studies over 19 publications (<jats:italic>n<\/jats:italic>\u2009=\u2009474 patients) were included. Lean body mass was unaffected in three studies (<jats:italic>n<\/jats:italic>\u2009=\u2009126) and increased by 1.8\u20131.92\u2009kg in two studies (<jats:italic>P<\/jats:italic>\u2009=\u20090.02 and 0.003, respectively; <jats:italic>n<\/jats:italic>\u2009=\u200948). Pioglitazone was associated with increased peripheral insulin sensitivity (+23%\u201372%, standardized mean difference of 0.97 from trial start point to end point [95% CI, 0.36\u20131.58; <jats:italic>n<\/jats:italic>\u2009=\u2009213]). Treatment reduced intramuscular tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) levels (\u221230%; <jats:italic>P<\/jats:italic>\u2009=\u20090.02; <jats:italic>n<\/jats:italic>\u2009=\u200929), with mixed effects on serum TNF\u2010\u03b1 and intramyocellular lipid concentrations. Treatment increased intramuscular markers of adenosine triphosphate (ATP) biosynthesis (ATP5A [+33%, <jats:italic>P<\/jats:italic>\u2009\u2264\u20090.05], ETFA [+60%, <jats:italic>P<\/jats:italic>\u2009\u2264\u20090.05], and CX6B1 [+\u200933%, <jats:italic>P<\/jats:italic>\u2009=\u20090.01] [<jats:italic>n<\/jats:italic>\u2009=\u200924]), PGC1\u03b1 and PGC1\u03b2 messenger RNA expression (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05; <jats:italic>n<\/jats:italic>\u2009=\u200926), and AMPK phosphorylation (+38%, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05; <jats:italic>n<\/jats:italic>\u2009=\u200926). These data have low\u2010quality evidence profiles owing to risk of bias.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Pioglitazone therapy increases skeletal muscle insulin sensitivity and can decrease intramuscular inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jpen.2481","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T04:42:55Z","timestamp":1674708175000},"page":"459-475","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Can pioglitazone be used for optimization of nutrition in critical illness? 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