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 1day and 2weeks of cold exposure. Cold exposure increased food intake by 62% after 2weeks but intake was not significantly increased after 1day. Intestinal wet mass was elevated after 1day and throughout the experiment. Absorption of arabinose rose by 20% after 1day in the cold and was 33% higher after 2weeks. Expression of claudin-2 increased after 1day 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.
The most rapid age-related decrease in insulin-stimulated glucose uptake in skeletal muscle occurs between 3 and 5 wk of age in rats. Therefore, we studied unstimulated, insulin-stimulated, and in vitro hypoxia-stimulated 2-deoxy-D-[G-3H]glucose (2-DG) uptake in isolated soleus, flexor digitorum brevis (FDB), and epitrochlearis muscles from rats at 21, 28, and 35 days of age. Age-related decrements in insulin- (approximately 40-60%) and hypoxia-stimulated (approximately 50%) 2-DG uptake occurred in all muscles, and most of the decline was evident by 28 days. Unstimulated 2-DG uptake declined significantly with advancing age in the epitrochlearis (73%) and FDB (60%) and tended to decrease in the soleus (38%). The time course and relative magnitude of these decrements were similar under unstimulated, insulin-stimulated, and hypoxic conditions. GLUT-4 protein concentration was unaltered by age in each muscle. These results indicate that a substantial age-related decrement in 2-DG uptake occurs in several limb muscles from rats at 21 vs. 28-35 days by a mechanism that is independent of GLUT-4 levels and not specific for the insulin-dependent pathway.
Recent studies of birds and bats demonstrate high passive (paracellular) absorption of nutrients. We hypothesized that a species with low paracellular absorption (mice) could increase absorption in response to increased energy demand. We predicted that mice exposed to cold would increase intestinal size to meet the increased energy demand, but in the short term these mice would increase paracellular absorption as well. We transferred mice from 21 to 5 °C and assessed absorption of radiolabeled L‐arabinose, a paracellular absorption probe, at 3 timepoints: prior to cold exposure; after 1 day of cold exposure; and after 2 weeks in the cold. We also assessed control mice kept at 21 °C. Mean gut size increased over the 2 week cold exposure, and this was accompanied by an increase in food consumption. Absorption of an L‐arabinose dose increased from 15.8% (prior to exposure) to 19.4% (P=0.006) after 1 day in the cold, and 21.5% (P<0.001) after 2 weeks exposure. We also assessed expression (qPCR) of tight junction proteins ZO‐1, Cldn2, Cldn4, and Cldn15, relative to housekeeping gene Eef1a1 in the medial intestine. Cldn2 was differentially expressed among treatment groups (P=0.02); however, there were no treatment‐induced differences in the expression of the other tight junction proteins. Our results suggest that mice may adjust tight junction “leakiness” to meet short‐term need for increased absorptive capacity.
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