Fat malabsorption in essential fatty acid-deficient mice is not due to impaired bile formation. Am J Physiol Gastrointest Liver Physiol 283: G900-G908, 2002; 10.1152/ajpgi.00094.2002.-Essential fatty acid (EFA) deficiency induces fat malabsorption, but the pathophysiological mechanism is unknown. Bile salts (BS) and EFA-rich biliary phospholipids affect dietary fat solubilization and chylomicron formation, respectively. We investigated whether altered biliary BS and/or phospholipid secretion

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... iate EFA deficiency-induced fat malabsorption in mice. Free virus breed (FVB) mice received EFA-containing (EFA ϩ ) or EFAdeficient (EFA Ϫ ) chow for 8 wk. Subsequently, fat absorption, bile flow, and bile composition were determined. Identical dietary experiments were performed in multidrug resistance gene-2-deficient [Mdr2 (Ϫ/Ϫ) ] mice, secreting phospholipidfree bile. After 8 wk, EFA Ϫ -fed wild-type [Mdr2 (ϩ/ϩ) ] and Mdr2 (Ϫ/Ϫ) mice were markedly EFA deficient [plasma triene (20:3n-9)-to-tetraene (20:4n-6) ratio Ͼ0.2]. Fat absorption decreased (70.1 Ϯ 4.2 vs. 99.1 Ϯ 0.3%, P Ͻ 0.001), but bile flow and biliary BS secretion increased in EFA Ϫ mice compared with EFA ϩ controls (4.87 Ϯ 0.36 vs. 2.87 Ϯ 0.29 l ⅐ min Ϫ1 ⅐ 100 g body wt Ϫ1 , P Ͻ 0.001, and 252 Ϯ 30 vs. 145 Ϯ 20 nmol ⅐ min Ϫ1 ⅐ 100 g body wt Ϫ1 , P Ͻ 0.001, respectively). BS composition was similar in EFA ϩ -and EFA Ϫ -fed mice. Similar to EFA Ϫ Mdr2 (ϩ/ϩ) mice, EFA Ϫ Mdr2 (Ϫ/Ϫ) mice developed fat malabsorption associated with twofold increase in bile flow and BS secretion. Fat malabsorption in EFA Ϫ mice is not due to impaired biliary BS or phospholipid secretion. We hypothesize that EFA deficiency affects intracellular processing of dietary fat by enterocytes. fat absorption; multidrug resistance gene-2; ATP-binding cassette; polyunsaturated fatty acids; phospholipid; bile salt ESSENTIAL FATTY ACID (EFA) deficiency (EFA Ϫ ) has been associated with several pathological consequences in humans and experimental animals, including fat malabsorption (1, 2, 15, 21, 28). The pathophysiological mechanisms underlying EFA Ϫ -induced fat malabsorption have not been elucidated. To address this issue, the consecutive intraluminal and intracellular steps in *A. Werner and D. M. Minich contributed equally to this work.