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Am J Physiol Gastrointest Liver Physiol 283: G900-G908, 2002; doi:10.1152/ajpgi.00094.2002
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Vol. 283, Issue 4, G900-G908, October 2002

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, and Henkjan J. Verkade

Center for Liver, Digestive, and Metabolic Diseases, Pediatric Gastroenterology, Department of Pediatrics, University Hospital, 9700 RB Groningen, The Netherlands

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.

fat absorption; multidrug resistance gene-2; ATP-binding cassette; polyunsaturated fatty acids; phospholipid; bile salt

* A. Werner and D. M. Minich contributed equally to this work.




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