Background: Asthma physiology affects respiratory function and inflammation, factors that may contribute to elevated resting energy expenditure (REE) and altered body composition. Objective: We hypothesized that asthma would present with elevated REE compared to weight-matched healthy controls. Methods: Adults with asthma (n = 41) and healthy controls (n = 20) underwent indirect calorimetry to measure REE, dual-energy X-ray absorptiometry (DEXA) to measure body composition, and 3-day diet records. Clinical assessments included spirometry, fractional exhaled nitric oxide (FENO), and a complete blood count. Results: Asthmatics had greater REE than controls amounting to an increase of ~100 kcals/day, even though body mass index (BMI) and body composition were similar between groups. Inclusion of asthma status and FENO in validated REE prediction equations led to improved estimates. Further, asthmatics had higher white blood cell (control vs. asthma (mean ± SD): 4.7 ± 1.1 vs. 5.9 ± 1.6, p < 0.01) and neutrophil (2.8 ± 0.9 vs. 3.6 ± 1.4, p = 0.02) counts that correlated with REE (both p < 0.01). Interestingly, despite higher REE, asthmatics reported consuming fewer calories (25.1 ± 7.5 vs. 20.3 ± 6.0 kcals/kg/day, p < 0.01) and carbohydrates than controls. Conclusion: REE is elevated in adults with mild asthma, suggesting there is an association between REE and the pathophysiology of asthma.

Background: Blood lipids are dysregulated in pulmonary hypertension (PH). Lower high-density lipoproteins cholesterol (HDL-C) and low-density lipoproteins cholesterol (LDL-C) are associated with disease severity and death in PH. Right ventricle (RV) dysfunction and failure are the major determinants of morbidity and mortality in PH. This study aims to test the hypothesis that dyslipidemia is associated with RV dysfunction in PH. Methods: We enrolled healthy control subjects (n=12) and individuals with PH (n=30) (age: 18-65 years old). Clinical characteristics, echocardiogram, 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (PET) scan, blood lipids, including total cholesterol (TC), triglycerides (TG), lipoproteins (LDL-C and HDL-C), and N-terminal pro-B type Natriuretic Peptide (NT-proBNP) were determined. Results: Individuals with PH had lower HDL-C [PH, 41±12; control, 56±16 mg/dL, p <0.01] and higher TG to HDL-C ratio [PH, 3.6±3.1; control, 2.2±2.2, p<0.01] as compared to controls. TC, TG, and LDL-C were similar between PH and controls. Lower TC and TG were associated with worse RV function measured by RV strain ( R =–0.43, p =0.02 and R= –0.37, p =0.05 respectively), RV fractional area change ( R =0.51, p <0.01 and R =0.48, p <0.01 respectively), RV end-systolic area ( R =–0.63, p <0.001 and R =–0.48, p <0.01 respectively), RV end-diastolic area: R =–0.58, p <0.001 and R =–0.41, p =0.03 respectively), and RV glucose uptake by PET ( R =–0.46, p =0.01 and R =–0.30, p =0.10 respectively). NT-proBNP was negatively correlated with TC ( R = – 0.61, p =0.01) and TG ( R =–0.62, p <0.02) in PH. Conclusion: These findings confirm dyslipidemia is associated with worse right ventricular function in PH.

Metabolic and bioenergetic abnormalities are associated with asthma, yet the mechanisms linking these disruptions to disease pathophysiology remain unclear. We hypothesized that asthma arises from altered connectivity within metabolic networks. To test this, we employed a systems-level approach integrating platelet bioenergetic profiling with plasma metabolomics to map the bioenergetic-metabolite interactome. Fasting plasma metabolites and platelet bioenergetics were analyzed in individuals with asthma (n = 40) and healthy controls (n = 18). Among 119 altered metabolites, adenosine derivatives correlated with inflammation, and lung function, but did not fully distinguish asthma from controls. Platelet bioenergetic profiling revealed less ATP-linked oxygen consumption, and greater bioenergetic reserve capacity in asthma. Studies of primary human airway smooth muscle cells identify less mitochondrial glucose use in asthma as compared with controls. Integration of platelet bioenergetics and plasma metabolites shows a restructured network in asthma with fewer connections between metabolites and bioenergetic nodes, and new asthma-specific clusters enriched in lipid metabolism. These findings reveal a previously unrecognized bioenergetic phenotype of asthma, defined by greater oxidative reserve capacity, less mitochondrial glucose utilization, and a shift of the bioenergetic - metabolic network toward lipid pathways.

• Mitochondrial ARG2 regulates arginine availability, nitric oxide levels, and fatty acid metabolism. • Mitochondrial ARG2 is a key regulator of hematopoietic and cardiovascular responses to acute and chronic hypoxia.

Background Metabolic surgery has beneficial metabolic effects, including remission of type 2 diabetes. We hypothesized that duodenojejunal bypass (DJB) surgery can protect against development of type 1 diabetes (T1D) by enhancing regulation of cellular and molecular pathways that control glucose homeostasis. Methods BBDP/Wor rats, which are prone to develop spontaneous autoimmune T1D, underwent loop DJB (n = 15) or sham (n = 15) surgery at a median age of 41 days, before development of diabetes. At T1D diagnosis, a subcutaneous insulin pellet was implanted, oral glucose tolerance test was performed 21 days later, and tissues were collected 25 days after onset of T1D. Pancreas and liver tissues were assessed by histology and RT-qPCR. Fecal microbiota composition was analyzed by 16S V4 sequencing. Results Postoperatively, DJB rats weighed less than sham rats (287.8 vs 329.9 g, P = 0.04). In both groups, 14 of 15 rats developed T1D, at similar age of onset (87 days in DJB vs 81 days in sham, P = 0.17). There was no difference in oral glucose tolerance, fasting and stimulated plasma insulin and c-peptide levels, and immunohistochemical analysis of insulin-positive cells in the pancreas. DJB rats needed 1.3 ± 0.4 insulin implants vs 1.9 ± 0.5 in sham rats (P = 0.002). Fasting and glucose stimulated glucagon-like peptide 1 (GLP-1) secretion was elevated after DJB surgery. DJB rats had reduced markers of metabolic stress in liver. After DJB, the fecal microbiome changed significantly, including increases in Akkermansia and Ruminococcus, while the changes were minimal in sham rats. Conclusion DJB does not protect against autoimmune T1D in BBDP/Wor rats, but reduces the need for exogenous insulin and facilitates other metabolic benefits including weight loss, increased GLP-1 secretion, reduced hepatic stress, and altered gut microbiome.