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

Abstract

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 mediate EFA deficiency-induced fat malabsorption in mice. Free virus breed (FVB) mice received EFA-containing (EFA+) or EFA-deficient (EFA−) 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(−/−)] mice, secreting phospholipid-free bile. After 8 wk, EFA−-fed wild-type [ Mdr2(+/+)] and Mdr2(−/−)mice were markedly EFA deficient [plasma triene (20:3n-9)-to-tetraene (20:4n-6) ratio >0.2]. Fat absorption decreased (70.1 ± 4.2 vs. 99.1 ± 0.3%, P < 0.001), but bile flow and biliary BS secretion increased in EFA−mice compared with EFA+controls (4.87 ± 0.36 vs. 2.87 ± 0.29 μl · min−1· 100 g body wt−1, P < 0.001, and 252 ± 30 vs. 145 ± 20 nmol · min−1· 100 g body wt−1, P < 0.001, respectively). BS composition was similar in EFA+- and EFA−-fed mice. Similar to EFA−Mdr2(+/+)mice, EFA−Mdr2(−/−)mice developed fat malabsorption associated with twofold increase in bile flow and BS secretion. Fat malabsorption in EFA−mice is not due to impaired biliary BS or phospholipid secretion. We hypothesize that EFA deficiency affects intracellular processing of dietary fat by enterocytes.