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Coronavirus disease 2019 (COVID‐19), the worst pandemic in more than a century, has claimed >125,000 lives worldwide to date. Emerging predictors for poor outcomes include advanced age, male sex, preexisting cardiovascular disease, and risk factors including hypertension, diabetes, and, more recently, obesity. This article posits new obesity‐driven predictors of poor COVID‐19 outcomes, over and above the more obvious extant risks associated with obesity, including cardiometabolic disease and hypoventilation syndrome in intensive care patients. This article also outlines a theoretical mechanistic framework whereby adipose tissue in individuals with obesity may act as a reservoir for more extensive viral spread, with increased shedding, immune activation, and cytokine amplification. This paper proposes studies to test this reservoir concept with a focus on specific cytokine pathways that might be amplified in individuals with obesity and COVID‐19. Finally, this paper underscores emerging therapeutic strategies that might benefit subsets of patients in which cytokine amplification is excessive and potentially fatal.

Objective There is compelling clinical evidence implicating certain dietary components in the development and clinical course of progression in ulcerative colitis (UC). This study aimed to assess whether any association exists between ulcerative colitis and scores on a healthy eating index. Methods In this case-control study patients with UC were recruited and assessed together with healthy controls. The participants completed a validated 168-item food frequency questionnaire, the results of which were subsequently used to generate individual healthy eating index (HEI-2015) scores. Results Altogether 58 patients with UC and 123 healthy controls were recruited. After controlling for confounding factors, participants who were in the highest quartile of the HEI-2015 had a 66% lower odds ratio (OR) of UC than the lowest quartile (OR = 0.34, 95% confidence interval 0.12-0.96). Conclusion HEI-2015 was associated with UC in this cohort. Further elucidation of the role of key dietary elements is now warranted.

Fibroblast growth factor-19 (FGF-19) is a gut hormone which interacts with metabolism and is depleted in obesity. There is some indication that the hormone undergoes a resurgence following bariatric surgery (BS), an effect which may contribute to the beneficial outcomes of such procedures. This systematic review and meta-analysis aims to synthesize the available literature on FGF-19 levels before and after BS. MEDLINE, Scopus and Web of Science databases were searched, and the effect of different surgical procedures and degrees of body mass index (BMI) reduction on FGF-19 levels was assessed by DerSimonian and Laird random-effects model in meta-analysis and dose-response analyses. This meta-analysis, which included 474 patients from 25 arms undergoing one of five BS procedures, revealed a significant increase in the levels of circulating FGF-19 following all-type BS. Vertical sleeve gastrectomy, duodenal-jejunal bypass liner and Roux-en-Y gastric bypass all significantly increased circulating FGF-19 levels from baseline. However, gastric banding failed to achieve the same, and in fact, biliopancreatic diversion was associated with decreased circulating FGF-19. Finally, an inverse association between FGF-19 and the degree of BMI-reduction post-operatively was noted. FGF-19 is increased by BS and may represent a pharmaceutical target in efforts to reproduce the beneficial effects of BS in a medical setting.

Chronic inflammation underlies many of the health decrements associated with obesity. Circulating progenitor cells can sense and respond to inflammatory stimuli, increasing the local inflammatory response within tissues. Here we show that 6 weeks of endurance exercise training significantly decreases inflammatory circulating progenitor cells in obese adults. These findings provide novel cellular mechanisms for the beneficial effects of exercise in obese adults.Circulating progenitor cells (CPCs) and subpopulations are normally found in the bone marrow, but can migrate to peripheral tissues to participate in local inflammation and/or remodelling. The purpose of this study was to compare the CPC response, particularly the inflammatory-primed haematopoietic stem and progenitor (HSPC) subpopulation, to a 6 week endurance exercise training (EET) intervention between lean and obese adults. Seventeen healthy weight (age: 23.9 ± 5.4 years, body mass index (BMI): 22.0 ± 2.6 kg m

The zinc-finger transcription factor, Mxr1 activates methanol utilization and peroxisome biogenesis genes in the methylotrophic yeast, Pichia pastoris. Expression of Mxr1-dependent genes is regulated in response to various carbon sources by an unknown mechanism. We show here that this mechanism involves the highly conserved 14-3-3 proteins. 14-3-3 proteins participate in many biological processes in different eukaryotes. We have characterized a putative 14-3-3 binding region at Mxr1 residues 212-225 and mapped the major activation domain of Mxr1 to residues 246-280, and showed that phenylalanine residues in this region are critical for its function. Furthermore, we report that a unique and previously uncharacterized 14-3-3 family protein in P. pastoris complements Saccharomyces cerevisiae 14-3-3 functions and interacts with Mxr1 through its 14-3-3 binding region via phosphorylation of Ser215 in a carbon source-dependent manner. Indeed, our in vivo results suggest a carbon source-dependent regulation of expression of Mxr1-activated genes by 14-3-3 in P. pastoris. Interestingly, we observed 14-3-3-independent binding of Mxr1 to the promoters, suggesting a post-DNA binding function of 14-3-3 in regulating transcription. We provide the first molecular explanation of carbon source-mediated regulation of Mxr1 activity, whose mechanism involves a post-DNA binding role of 14-3-3.

Chronic hypoxia in the gestating fetus is a common occurrence which invariably leads to a variety of adverse events such as premature delivery, pulmonary hypertension, intrauterine growth restriction (IUGR) and fetal/adult cardiovascular dysfunction. This article is protected by copyright. All rights reserved