Essential fatty acid deficiency in mice impairs lactose digestion

Abstract

Essential fatty acid (EFA) deficiency in mice induces fat malabsorption. We previously reported indications that the underlying mechanism is located at the level of the intestinal mucosa. We have investigated the effects of EFA deficiency on small intestinal morphology and function. Mice were fed an EFA-deficient or control diet for 8 wk. A 72-h fat balance, the EFA status, and small intestinal histology were determined. Carbohydrate absorptive and digestive capacities were assessed by stable isotope methodology after administration of [U-(13)C]glucose and [1-(13)C]lactose. The mRNA expression and enzyme activity of lactase, and concentrations of the EFA linoleic acid (LA) were measured in small intestinal mucosa. Mice fed the EFA-deficient diet were markedly EFA-deficient with a profound fat malabsorption. EFA deficiency did not affect the histology or proliferative capacity of the small intestine. Blood [13C6]glucose appearance and disappearance were similar in both groups, indicating unaffected monosaccharide absorption. In contrast, blood appearance of [13C]glucose, originating from [1-(13)C]lactose, was delayed in EFA-deficient mice. EFA deficiency profoundly reduced lactase activity (-58%, P<0.01) and mRNA expression (-55%, P<0.01) in mid-small intestine. Both lactase activity and its mRNA expression strongly correlated with mucosal LA concentrations (r=0.77 and 0.79, respectively, P<0.01). EFA deficiency in mice inhibits the capacity to digest lactose but does not affect small intestinal histology. These data underscore the observation that EFA deficiency functionally impairs the small intestine, which in part may be mediated by low LA levels in the enterocytes.

Lactose maldigestion during methotrexate-induced gastrointestinal mucositis in a rat model

“…Hematoxylin and eosin (H&E) staining was done on 3-m-thick sections of formalin-and PFA-fixed jejunal segments to assess histology, according to standard procedures. Morphometric analysis was carried out as described previously (20). Villus and crypt length were measured manually in well-orientated sections (10 measurements/rat) from digitized images that were evaluated at ϫ10 magnification (1 pixel ϭ 0.397 m) using a calibrated image analysis system (Qwin V3.0; Leica Microsystems).…”

“…[ (35) by gas chromatography-mass spectometry (Agilent 5957C Series GC/MSD; Agilent Technologies, Amstelveen, The Netherlands) as has been done previously (20). The calculations for blood glucose kinetics were described recently by Van Dijk (34) and Laskewitz (18).…”

“…Mucosa of frozen duodenal, jejunal, and ileal sections was scraped on ice to make tissue homogenates in distilled water. Homogenates were 100 -400 times diluted before glycohydrolase activity levels were measured of lactase, sucrase, isomaltase, and maltase as described previously (7,20). Activ-ity levels were normalized to protein levels that were measured by the BCA method as described by the manufacturer (BCA protein assay kit; Thermo Fischer Scientific, Rockford, IL).…”

Effects of essential fatty acid deficiency on enterohepatic circulation of bile salts in mice

“…Bile salts are essential for bile production, secretory processes, and efficient intestinal absorption of dietary fat. In our laboratory we developed a mouse model to study the effects of EFA deficiency in vivo (31,49). Previous studies in this mouse model have shown that EFA deficiency-associated fat malabsorption is not caused by impaired bile formation, as has been implied earlier in a rat model for EFA deficiency (28).…”

“…4141.08) and EFA-sufficient (control, no. 4141.07) diets (16 wt% and 34 energy% fat), which were custom synthesized by Arie Bloks (Woerden, the Netherlands) (31,49). Essentially, unsaturated fatty acids in EFA-sufficient diet were replaced by saturated fatty acid in an EFA-deficient diet; the EFA-deficient diet was particularly reduced in linoleic acid (essential fatty acid) concentration.…”