Adipokine C1q/Tumor Necrosis Factor- Related Protein 3 (CTRP3) Attenuates Intestinal Inflammation Via Sirtuin 1/NF-κB Signaling.

BACKGROUND & AIMS: The adipokine CTRP3 has anti-inflammatory effects in several nonintestinal disorders. Although serum CTRP3 is reduced in patients with inflammatory bowel disease (IBD), its function in IBD has not been established. Here, we elucidate the function of CTRP3 in intestinal inflammation. METHODS: CTRP3 knockout (KO) and overexpressing transgenic (Tg) mice, along with their corresponding wild-type littermates, were treated with dextran sulfate sodium for 6-10 days. Colitis phenotypes and histologic data were analyzed. CTRP3-mediated signaling was examined in murine and human intestinal mucosa and mouse intestinal organoids derived from CTRP3 KO and Tg mice. RESULTS: CTRP3 KO mice developed more severe colitis, whereas CTRP3 Tg mice developed less severe colitis than wild-type littermates. The deletion of CTRP3 correlated with decreased levels of Sirtuin-1 (SIRT1), a histone deacetylase, and increased levels of phosphorylated/acetylated NF-κB subunit p65 and proinflammatory cytokines tumor necrosis factor-α and interleukin-6. Results from CTRP3 Tg mice were inverse to those from CTRP3 KO mice. The addition of SIRT1 activator resveratrol to KO intestinal organoids and SIRT1 inhibitor Ex-527 to Tg intestinal organoids suggest that SIRT1 is a downstream effector of CTRP3-related inflammatory changes. In patients with IBD, a similar CTRP3/SIRT1/NF-κB relationship was observed. CONCLUSIONS: CTRP3 expression levels correlate negatively with intestinal inflammation in acute mouse colitis models and patients with IBD. CTRP3 may attenuate intestinal inflammation via SIRT1/NF-κB signaling. The manipulation of CTRP3 signaling, including through the use of SIRT1 activators, may offer translational potential in the treatment of IBD.

Malnutrition Increases Hospital Length of Stay and Mortality among Adult Inpatients with COVID-19.

Background: Malnutrition has been linked to adverse health economic outcomes. There is a paucity of data on malnutrition in patients admitted with COVID-19. Methods: This is a retrospective cohort study consisting of 4311 COVID-19 adult (18 years and older) inpatients at 5 Johns Hopkins-affiliated hospitals between 1 March and 3 December 2020. Malnourishment was identified using the malnutrition universal screening tool (MUST), then confirmed by registered dietitians. Statistics were conducted with SAS v9.4 (Cary, NC, USA) software to examine the effect of malnutrition on mortality and hospital length of stay among COVID-19 inpatient encounters, while accounting for possible covariates in regression analysis predicting mortality or the log-transformed length of stay. Results: COVID-19 patients who were older, male, or had lower BMIs had a higher likelihood of mortality. Patients with malnutrition were 76% more likely to have mortality (p < 0.001) and to have a 105% longer hospital length of stay (p < 0.001). Overall, 12.9% (555/4311) of adult COVID-19 patients were diagnosed with malnutrition and were associated with an 87.9% increase in hospital length of stay (p < 0.001). Conclusions: In a cohort of COVID-19 adult inpatients, malnutrition was associated with a higher likelihood of mortality and increased hospital length of stay.