Paracellular absorption in laboratory mice: Molecule size-dependent but low capacity

Journal of Experimental Biology

Rott

Caviedes‐Vidal

et al. 2014

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Flying vertebrates have been hypothesized to rely heavily on paracellular absorption of nutrients to compensate for having smaller intestines than non-flyers. We tested this hypothesis in an insectivorous bat (Myotis lucifugus) and two insect-eating rodents (Onychomys leucogaster and Peromyscus leucopus). In intact animals, the fractional absorption of orally dosed L-arabinose (M r 150) was 82% in M. lucifugus, which was more than twice that of the rodents. Absorption of creatinine (M r 113) was greater than 50% for all species and did not differ between M. lucifugus and the rodents. We also conducted intestinal luminal perfusions on anesthetized animals. Absorption of L-arabinose per nominal surface area in M. lucifugus was nearly double that of the rodents, while absorption of creatinine was not different among species. Using an everted sleeve preparation, we demonstrated that high concentrations of L-arabinose and creatinine did not inhibit their own uptake, validating their use as passive, paracellular probes. Histological measurements indicated that M. lucifugus has more cells, and presumably more tight junctions, per nominal surface area than P. leucopus. This seems unlikely to explain entirely the higher absorption of L-arabinose in M. lucifugus during perfusions, because L-arabinose absorption normalized to the number of enterocytes was still double that of P. leucopus. As an alternative, we investigated tight junction gene expression. M. lucifugus had higher expression of claudin-1 and claudin-15, and lower expression of claudin-2 relative to P. leucopus. Expression of claudin-7 and occludin did not differ among species. Taken together, our results support the hypothesis that bats have evolved higher paracellular nutrient absorption than non-flying animals, and that this phenomenon might be driven by both histological characteristics and differences in tight junction gene expression.

Section: Whole Animal Paracellular Nutrient Absorptionsupporting

confidence: 89%

Section: Whole Animal Paracellular Nutrient Absorptionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

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Paracellular nutrient absorption is higher in bats than rodents: integrating from intact animals to the molecular level

Journal of Experimental Biology

Rott

Caviedes‐Vidal

et al. 2014

Self Cite

“…Mice were then placed in the metabolic chambers (20cm diameter by 10cm height) and we collected the urine that was produced after 90, 180, 270 and 1200min following dosing. Previous work showed that this time period is long enough to measure fractional absorption of arabinose (Fasulo et al, 2013a ]-L-arabinose recoveries by 1.11 to account for this difference in probe recovery, producing an 'adjusted cumulative % injection dose recovered'. Although L-arabinose is not metabolized and theoretically can be fully recovered, recoveries of injected inert probes are often less than 100% (Karasov et al, 2012).…”

Section: Assessment Of L-arabinose Fractional Absorptionmentioning

confidence: 99%

“…Paracellular absorption is size and charge selective, and may be driven by solvent drag (as water passes through the tight junctions) and/or via simple diffusion of the molecules (Pappenheimer and Reiss, 1987;Fine et al, 1994;Chediack et al, 2003;Chediack et al, 2006). Absorption via the paracellular route often represents a low proportion of total nutrient absorption in humans, mice and other non-flying mammals (Delahunty and Hollander, 1987;Fasulo et al, 2013a), and this prevents other nontarget molecules, e.g. small water-soluble toxins, from gaining access to the circulation (Diamond, 1991).…”

Section: Introductionmentioning

confidence: 99%

Cold exposure increases intestinal paracellular permeability to nutrients in the mouse

Journal of Experimental Biology

Ruff

Guerra

et al. 2013

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SUMMARYIn situations of increased energy demand and food intake, animals can often acclimate within several days. The intestine generally responds to elevated digestive demand by increasing in size. However, there is likely a limit to how quickly the intestine can grow to meet the new demand. We investigated the immediate and longer-term changes to intestinal properties of the mouse when suddenly exposed to 4°C. We hypothesized that paracellular permeability to nutrients would increase as part of an immediate response to elevated absorptive demand. We measured absorption of L-arabinose, intestinal size and gene expression of several tight junction proteins (claudin-2, claudin-4, claudin-15 and ZO-1) at three time points: pre-exposure, and after 1day and 2weeks of cold exposure. Cold exposure increased food intake by 62% after 2weeks but intake was not significantly increased after 1day. Intestinal wet mass was elevated after 1day and throughout the experiment. Absorption of arabinose rose by 20% after 1day in the cold and was 33% higher after 2weeks. Expression of claudin-2 increased after 1day of cold exposure, but there were no changes in expression of any claudin genes when normalized to ZO-1 expression. Our results indicate that intestinal mass can respond rapidly to increased energy demand and that increased paracellular permeability is also part of that response. Increased paracellular permeability may be a consequence of enterocyte hyperplasia, resulting in more tight junctions across which molecules can absorb.

A Comparison of mucosal surface area and villous histology in small intestines of the Brazilian free‐tailed bat (Tadarida brasiliensis) and the mouse (Mus musculus)

Zhang

Brun

et al. 2014

Journal of Morphology

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Studies on birds have led to the hypothesis that increased intestinal absorption between enterocytes (paracellular) evolved as a compensation for smaller intestinal size in fliers, which was perhaps selected to minimize the mass of digesta carried. This hypothesis predicts that bats will also exhibit relatively reduced intestinal size and high paracellular absorption, compared with nonflying mammals. Published studies on three bat species indicate relatively high paracellular absorption. One mechanism for increasing paracellular absorption per cm2 small intestine (SI) is increased number of tight junctions (TJs) across which paracellular absorption occurs. To our knowledge, we provide the first comparative analysis of enterocyte size and number in flying and nonflying mammals. Intestines of insectivorous bats Tadarida brasiliensis were compared with Mus musculus using hematoxylin and eosin staining method. Bats had shorter and narrower SIs than mice, and after correction for body size difference by normalizing to mass3/4, the bats had 40% less nominal surface area than the mouse, as predicted. Villous enhancement of surface area was 90% greater in the bat than in the mouse, mainly because of longer villi and a greater density of villi in bat intestines. Bat and mouse were similar in enterocyte diameter. Bats exceeded mice by 54.4% in villous area per cm length SI and by 95% in number of enterocytes per cm2 of the nominal surface area of the SI. Therefore, an increased density of TJs per cm2 SI may be a mechanistic explanation that helps to understand the high paracellular absorption observed in bats compared to nonflying mammals.