Fat malabsorption in essential fatty acid-deficient mice is not due to impaired bile formation

Anniek Werner, Deanna M. Minich, Rick Havinga, Vincent Bloks, Harry Van Goor, Folkert Kuipers, Henkjan J. Verkade
2002 American Journal of Physiology - Gastrointestinal and Liver Physiology  
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
more » ... 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.
doi:10.1152/ajpgi.00094.2002 pmid:12223350 fatcat:earvv7bjhbbvnjjgg7swqm7vke