A Specialized Epithelial Cell Type Regulating Mucosal Immunity and Driving Human Crohn's Disease.

Crohn's disease (CD) is a complex chronic inflammatory disorder that may affect any part of gastrointestinal tract with extra-intestinal manifestations and associated immune dysregulation. To characterize heterogeneity in CD, we profiled single-cell transcriptomics of 170 samples from 65 CD patients and 18 non-inflammatory bowel disease (IBD) controls in both the terminal ileum (TI) and ascending colon (AC). Analysis of 202,359 cells identified a novel epithelial cell type in both TI and AC, featuring high expression of LCN2, NOS2, and DUOX2, and thus is named LND. LND cells, confirmed by high-resolution in-situ RNA imaging, were rarely found in non-IBD controls, but expanded significantly in active CD. Compared to other epithelial cells, genes defining LND cells were enriched in antimicrobial response and immunoregulation. Moreover, multiplexed protein imaging demonstrated that LND cell abundance was associated with immune infiltration. Cross-talk between LND and immune cells was explored by ligand-receptor interactions and further evidenced by their spatial colocalization. LND cells showed significant enrichment of expression specificity of IBD/CD susceptibility genes, revealing its role in immunopathogenesis of CD. Investigating lineage relationships of epithelial cells detected two LND cell subpopulations with different origins and developmental potential, early and late LND. The ratio of the late to early LND cells was related to anti-TNF response. These findings emphasize the pathogenic role of the specialized LND cell type in both Crohn's ileitis and Crohn's colitis and identify novel biomarkers associated with disease activity and treatment response.

Aerobic exercise training improves hepatic and muscle insulin sensitivity, but reduces splanchnic glucose uptake in obese humans with type 2 diabetes.

BACKGROUND: Aerobic exercise training is known to have beneficial effects on whole-body glucose metabolism in people with type 2 diabetes (T2D). The responses of the liver to such training are less well understood. The purpose of this study was to determine the effect of aerobic exercise training on splanchnic glucose uptake (SGU) and insulin-mediated suppression of endogenous glucose production (EGP) in obese subjects with T2D. METHODS: Participants included 11 obese humans with T2D, who underwent 15 ± 2 weeks of aerobic exercise training (AEX; n = 6) or remained sedentary for 15 ± 1 weeks (SED; n = 5). After an initial screening visit, each subject underwent an oral glucose load clamp and an isoglycemic/two-step (20 and 40 mU/m2/min) hyperinsulinemic clamp (ISO-clamp) to assess SGU and insulin-mediated suppression of EGP, respectively. After the intervention period, both tests were repeated. RESULTS: In AEX, the ability of insulin to suppress EGP was improved during both the low (69 ± 9 and 80 ± 6% suppression; pre-post, respectively; p < 0.05) and high (67 ± 6 and 82 ± 4% suppression, respectively; p < 0.05) insulin infusion periods. Despite markedly improved muscle insulin sensitivity, SGU was reduced in AEX after training (22.9 ± 3.3 and 9.1 ± 6.0 g pre-post in AEX, respectively; p < 0.05). CONCLUSIONS: In obese T2D subjects, exercise training improves whole-body glucose metabolism, in part, by improving insulin-mediated suppression of EGP and enhancing muscle glucose uptake, which occur despite reduced SGU during an oral glucose challenge.

Oxygen Consumption during Viniyoga Practice in Adults.

CONTEXT: The purpose of this study was to measure the oxygen consumption (V̇O2) during Viniyoga yoga movements (asanas) and to compare V̇O2 walking among adults. METHODS: Yoga practitioners (n = 10) were recruited to measure V̇O2 while at rest (30 min), practicing yoga (16 movements with different variations), and treadmill walking at 2 mph (10 min) and 3 mph (10 min). V̇O2 was measured using a whole-room indirect calorimetry. Each yoga movement was categorized by body orientation as standing, lying, and sitting. The differences in V̇O2 between yoga and walking were examined using Pearson's correlations. Differences in V̇O2 between poses (standing, sitting, and lying) were examined using linear regression models. V̇O2. RESULTS: Mean yoga-V̇O2 for the entire yoga session was 3.7 (standard deviation [SD] 0.43, range: 4.4-8.9) ml/kg/min. Yoga-V̇O2 varied by body orientation: standing = 7.5 (SD = 1.5) ml/kg/min, lying = 5.3 (SD = 1.0) ml/kg/min, and sitting = 5.4 (SD = 1.1) ml/kg/min. After adjusting for body mass, frequency of yoga practice, and resting energy expenditure, female gender was negatively associated with mean yoga V̇O2 for standing (B = -112.19, P < 0.05), lying (B = -141.87, P < 0.05), and sitting (B = -129.96, P < 0.05). Mean V̇O2 for walking 2 mph was comparable with sitting (r = 0.836, P < 0.05) and lying (r = 0.735, P < 0.05) whereas walking at 3 mph was comparable with standing (r = 0.718, P < 0.05) and sitting (r = 0.760, P < 0.05). CONCLUSION: We conclude that V̇O2 during yoga practice is comparable to V̇O2 during slow treadmill walking and may vary based on gender and body orientation.