Our findings show that, in human obesity, plasma visfatin is reduced, whereas visfatin mRNA is differentially regulated in SAT and VAT. Visfatin is not related to insulin resistance either as assessed by homeostasis model assessment or during lipid infusion.

Insulin resistance and obesity are associated with a reduction of mitochondrial content in various tissues of mammals. Moreover, a reduced nitric oxide (NO) bioavailability impairs several cellular functions, including mitochondrial biogenesis and insulin-stimulated glucose uptake, two important mechanisms of body adaptation in response to physical exercise. Although these mechanisms have been thoroughly investigated in skeletal muscle and heart, few studies have focused on the effects of exercise on mitochondria and glucose metabolism in adipose tissue. In this study, we compared the in vivo effects of chronic exercise in subcutaneous adipose tissue of wild-type (WT) and endothelial NO synthase (eNOS) knockout (eNOS 2/2 ) mice after a swim training period. We then investigated the in vitro effects of NO on mouse 3T3-L1 and human subcutaneous adipose tissue-derived adipocytes after a chronic treatment with an NO donor: diethylenetriamine-NO (DETA-NO). We observed that swim training increases mitochondrial biogenesis, mitochondrial DNA content, and glucose uptake in subcutaneous adipose tissue of WT but not eNOS 2/2 mice. Furthermore, we observed that DETA-NO promotes mitochondrial biogenesis and elongation, glucose uptake, and GLUT4 translocation in cultured murine and human adipocytes. These results point to the crucial role of the eNOS-derived NO in the metabolic adaptation of subcutaneous adipose tissue to exercise training.Reduced mitochondrial content and/or activity is associated with impaired cell function in several diseases (1,2). In particular, it has been hypothesized that mitochondrial impairment may be involved in the pathogenesis of obesity and insulin resistance and their progression toward type 2 diabetes (3,4), even though the role of mitochondria in health and disease is still under discussion (5,6). At the same time, metabolic disorders are also associated with a reduction of endothelial nitric oxide synthase (eNOS) enzymatic activity (7,8); in fact, mice lacking the eNOS gene are considered a useful murine model for metabolic syndrome because they display typical features, including hypertension, hypertriglyceridemia, endothelial dysfunction, insulin resistance, and visceral obesity (9). It is well known that physical exercise induces profound physiological adaptations in several tissues as a response to increased metabolic requirements. One of the major events induced by physical activity is the upregulation of eNOS gene expression and the consequent

Objective The clinical manifestations of coronavirus disease (COVID‐19) run from asymptomatic disease to severe acute respiratory syndrome. Older age and comorbidities are associated to more severe disease. A role of obesity is suspected. Methods Patients hospitalized in the medical COVID‐19 ward with severe acute respiratory syndrome coronavirus 2–related pneumonia were enrolled. The primary outcome of the study was to assess the relationship between the severity of COVID‐19 and obesity classes according to BMI. Results A total of 92 patients (61.9% males; age 70.5 [13.3] years) were enrolled. Patients with overweight and obesity were younger than patients with normal weight (68.0 [12.6] and 67.0 [12.6] years vs. 76.1 [13.0] years, P < 0.01). A higher need for assisted ventilation beyond pure oxygen support (invasive mechanical ventilation or noninvasive ventilation) and a higher admission to intensive or semi‐intensive care units were observed in patients with overweight and obesity (P < 0.01 and P < 0.05, respectively) even after adjusting for sex, age, and comorbidities (P < 0.05 and P < 0.001, respectively) or when patients with dementia or advanced cancer were removed from the analysis (P < 0.05). Conclusions Patients with overweight and obesity admitted in a medical ward for severe acute respiratory syndrome coronavirus 2–related pneumonia, despite their younger age, required more frequently assisted ventilation and access to intensive or semi‐intensive care units than normal weight patients.

Background: The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a relevant threat for humans worldwide. Abnormality in liver function tests (LFTs) has been commonly observed in patients with COVID-19, but there is controversy on its clinical significance. The aim of this study was to assess the prevalence, the characteristics and the clinical impact of abnormal LFTs in hospitalized, non-critically ill patients with COVID-19. Methods: In this multicentre, retrospective study, we collected data about 565 inpatients with COVID-19. Data on LFTs were collected at admission and every 7 ± 2 days during the hospitalization. The primary outcome was a composite endpoint of death or transfer to intensive care unit (ICU). Results: Upon admission 329 patients (58%) had LFTs abnormality. Patients with abnormal LFTs had more severe inflammation and higher degree of organ dysfunction than those without. During hospitalization, patients with abnormal LFTs had a higher rate of transfer to ICU (20% vs 8%; P < .001), acute kidney injury (22% vs 13%, P = .009), need for mechanical ventilation (14% vs 6%; P = .005) and mortality (21% vs 11%; P = .004) than those without. In multivariate analysis, patients with abnormal LFTs had a higher risk of the composite endpoint of death or transfer to ICU (OR = 3.53; P < .001). During the hospitalization, 86 patients developed de novo LFTs abnormality, which was associated with the use of tocilizumab, lopinavir/ritonavir and acetaminophen and not clearly associated with the composite endpoint. | 2395 PIANO et Al.

Infection transmission from donor to recipient is a dreadful complication in transplantation. Although bacteremia was previously detected in 5% of donors without negative impact on recipient outcome, the current expansion of graft pool requires consideration of the infectious risk associated with suboptimal donors. This study aims to evaluate the incidence and risk factors of infection in unselected cadaveric liver donors, the occurrence of microorganism transmission to recipient and its influence on patient survival. Results of microbiologic cultures obtained before harvesting in intensive care unit (ICU) and routinely at harvesting from 610 consecutive liver donors were retrospectively analyzed. Evidence for bacterial and fungal transmission to the recipient was searched for in each culture-positive donor. One or more cultures were positive in 293 donors (48%), while bacteremia was present in 128 (21%). Culture-positive and bacteremic donors were of significantly older age and had longer ICU stays. At multivariate analysis, an ICU stay of 3 or more days was the only significant predictor of donor infection. Although 1-year patient/graft survival rates were not influenced by donor culture positivity, pathogen transmission occurred in 11 cases with high recipient 1-year mortality (45%). In those 11 cases, median donor age was 74 years, significantly much older than that of the other culture-positive donors. In conclusion, donors with a prolonged ICU stay are at increased risk of infection, while older donor age is associated with pathogen transmission to the recipient. Adequate donor maintenance and careful microbiologic surveillance and treatment, especially of elderly donors, may limit transmission of donor infection.

Endurance exercise training increases cardiac energy metabolism through poorly understood mechanisms. Nitric oxide (NO) produced by endothelial NO synthase (eNOS) in cardiomyocytes contributes to cardiac adaptation. Here we demonstrate that the NO donor diethylenetriamine-NO (DETA-NO) activated mitochondrial biogenesis and function, as assessed by upregulated peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A (Tfam) expression, and by increased mitochondrial DNA content and citrate synthase activity in primary mouse cardiomyocytes. DETA-NO also induced mitochondrial biogenesis and function and enhanced both basal and insulin-stimulated glucose uptake in HL-1 cardiomyocytes. The DETA-NO-mediated effects were suppressed by either PGC-1α or Tfam small-interference RNA in HL-1 cardiomyocytes. Wild-type and eNOS(-/-) mice were subjected to 6 wk graduated swim training. We found that eNOS expression, mitochondrial biogenesis, mitochondrial volume density and number, and both basal and insulin-stimulated glucose uptake were increased in left ventricles of swim-trained wild-type mice. On the contrary, the genetic deletion of eNOS prevented all these adaptive phenomena. Our findings demonstrate that exercise training promotes eNOS-dependent mitochondrial biogenesis in heart, which behaves as an essential step in cardiac glucose transport.

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OBJECTIVE -The aim of this study was to provide a comprehensive meta-analysis of randomized controlled clinical studies on the effects of sibutramine on weight loss and glycemic control in obese subjects with type 2 diabetes.RESEARCH DESIGN AND METHODS -Controlled clinical trials assessing the effect sizes of sibutramine on weight loss effects on glycemia in obese subjects with type 2 diabetes were identified and reviewed using the Cochrane Library, Medline, EMBASE, and a manual search.RESULTS -Eight placebo-controlled, double-blind, randomized trials of sibutramine were included. After sibutramine treatment, the decrease in body weight and waist circumference was significantly greater than in the placebo group. Fasting blood glucose and HbA 1c significantly decreased after sibutramine treatment. Treatment benefits were seen in plasma triglycerides and HDL, without significant variations in serum total and LDL cholesterol. No differences in systolic blood pressure between the sibutramine and the placebo groups were seen, while recording of diastolic blood pressure and heart rate showed that sibutramine produced a small increase relative to placebo.CONCLUSIONS -A pharmacological approach in a weight management program for patients with type 2 diabetes may be helpful in glycemic control and in the management of other risk factors. Sibutramine may help improve glucose control because it is conducive to weight loss. The reviewed data on the effect of sibutramine further enforce the recommendations that weight management may be the most important therapeutic task for most obese subjects with type 2 diabetes. Diabetes Care 28:942-949, 2005O besity has become a major public health concern not only in western societies but also in some developing countries and is reaching epidemic proportions. American adults have experienced a 50% increase in the prevalence of overweight and obesity, while children and adolescents have experienced a 100% increase since the 1970s (1). Coincident with this increase in obesity, the prevalence of type 2 diabetes has also reached epidemic proportions. About 50 million Americans exhibit metabolic syndrome, as defined in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2). It is noteworthy that the overall prevalence of the metabolic syndrome in nondiabetic adult Europeans is 15%, with the metabolic syndrome increasing the risk of death from all causes as well as cardiovascular disease (3). The U.K. Prospective Diabetes Study provided several outcomes that can be categorized as POEM (patient-oriented evidence that matters) (4). Among them, weight loss is especially challenging for insulin-or sulfonylurea-treated diabetic patients because this therapeutical approach has been found to cause weight gain without any impact on individual or aggregate microvascular or macrovascular outcomes (5). In fact, weight gain occurred in all patients except those treated with metformin. In overweight patie...