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White adipose tissue (WAT) lipolysis releases free fatty acids as a key energy substance to support metabolism in fasting, cold exposure, and exercise. Atgl, in concert with Cgi‐58, catalyzes the first lipolytic reaction. The sympathetic nervous system (SNS) stimulates lipolysis via neurotransmitter norepinephrine that activates adipocyte β adrenergic receptors (Adrb1‐3). In obesity, adipose Adrb signaling and lipolysis are impaired, contributing to pathogenic WAT expansion; however, the underling mechanism remains poorly understood. Recent studies highlight importance of N6‐methyladenosine (m6A)‐based RNA modification in health and disease. METTL14 heterodimerizes with METTL3 to form an RNA methyltransferase complex that installs m6A in transcripts. Here, this work shows that adipose Mettl3 and Mettl14 are influenced by fasting, refeeding, and insulin, and are upregulated in high fat diet (HFD) induced obesity. Adipose Adrb2, Adrb3, Atgl, and Cgi‐58 transcript m6A contents are elevated in obesity. Mettl14 ablation decreases these transcripts' m6A contents and increases their translations and protein levels in adipocytes, thereby increasing Adrb signaling and lipolysis. Mice with adipocyte‐specific deletion of Mettl14 are resistant to HFD‐induced obesity, insulin resistance, glucose intolerance, and nonalcoholic fatty liver disease (NAFLD). These results unravel a METTL14/m6A/translation pathway governing Adrb signaling and lipolysis. METTL14/m6A‐based epitranscriptomic reprogramming impairs adipose Adrb signaling and lipolysis, promoting obesity, NAFLD, and metabolic disease. [ABSTRACT FROM AUTHOR]

Increased morbidity and mortality from coronavirus disease 2019 (COVID-19) in people with obesity have illuminated the intersection of obesity with impaired responses to infections. Although data on mechanisms by which COVID-19 impacts health are being rapidly generated, there is a critical need to better understand the pulmonary, vascular, metabolic, and immunologic aspects that drive the increased risk for complications from COVID-19 in people with obesity. This review provides a broad overview of the intersection between COVID-19 and the physiology of obesity in order to highlight potential mechanisms by which COVID-19 disease severity is increased by obesity and identify areas for future investigation toward developing tailored therapy for people with obesity who develop COVID-19. [ABSTRACT FROM AUTHOR]

Dysfunctional adipose tissue plays a central role in the pathogenesis of the obesity‐related metabolic disease, including type 2 diabetes. Targeting adipose tissue using biopolymer implants is a novel therapeutic approach for metabolic disease. We transplanted porous poly(lactide‐co‐glycolide) (PLG) implants coated with human interleukin‐4 (hIL‐4)‐expressing lentivirus into epididymal white adipose tissue (eWAT) of mice fed a high‐fat diet. Tissue and systemic inflammation and metabolism were studied with flow cytometry, immunohistochemistry, quantitative real‐time polymerase chain reaction, adipose tissue histology, and in vivo glucose tolerance testing at 2 and 10 weeks of a high‐fat diet. PLG implants carrying hIL‐4‐expressing lentivirus implanted into epididymal white adipose tissue of mice‐regulated adipose tissue inflammation, including increased CD3+CD4+ T‐cell frequency, increased eWAT adipocyte hypertrophy, and decreased FASN and ATGL expression, along with reduced fasting blood glucose levels. These effects were observed in early obesity but were not maintained in established obesity. Local delivery of bioimplants loaded with cytokine‐expressing lentivirus vectors to adipose tissue influences tissue inflammation and systemic metabolism in early obesity. Further study will be required to show more durable metabolic effects. These data demonstrate that polymer biomaterials implanted into adipose tissue have the potential to modulate local tissue and systemic inflammation and metabolism. [ABSTRACT FROM AUTHOR]

Objective: The relationship between adipose tissue fibrosis, adipocyte hypertrophy, and preadipocyte hyperplasia in the context of obesity and the correlation of these tissue-based phenomena with systemic metabolic disease are poorly defined. The goal of this study was to clarify the relationship between adipose tissue fibrosis, adipocyte hypertrophy, and preadipocyte hyperplasia in human obesity and determine the correlation of these adipose-tissue based phenomena with diabetes.Methods: Visceral and subcutaneous adipose tissues from humans with obesity collected during bariatric surgery were studied with QRTPCR, immunohistochemistry, and flow cytometry for expression of collagens and fibrosis-related proteins, adipocyte size, and preadipocyte frequency. Results were correlated with clinical characteristics including diabetes status.Results: Fibrosis was decreased, hypertrophy was increased, and preadipocyte frequency and fibrotic gene expression were decreased in adipose tissues from diabetic subjects compared to non-diabetic subjects. These differences were greater in visceral compared to subcutaneous adipose tissue.Conclusions: These data are consistent with the hypothesis that adipose tissue fibrosis in the context of human obesity limits adipocyte hypertrophy and is associated with a reciprocal increase in adipocyte hyperplasia, with beneficial effects on systemic metabolism. These findings suggest adipose tissue fibrosis as a potential target for manipulation of adipocyte metabolism. [ABSTRACT FROM AUTHOR]

Objective Natural killer (NK) cells are understudied in the context of metabolic disease and obesity. The goal of this study was to define the effect of NK cell ablation on systemic inflammation and glucose homeostasis in murine obesity. Methods A transgenic murine model was used to study the effect of NK cell ablation on systemic inflammation and glucose homeostasis in the context of diet-induced obesity using flow cytometry, QRTPCR, and glucose tolerance and insulin sensitivity testing. Results NK cell ablation achieved a three to fourfold decrease in NK cells but had no effect on T-cell levels in adipose tissues and spleen. NK cell ablation was associated with decreased total macrophage infiltration in intra-abdominal adipose tissue, but macrophage infiltration in subcutaneous adipose tissue and spleen was unaffected. NK cell ablation was associated with modest improvement in insulin sensitivity but had no effect on tissue transcript levels of inflammatory cytokines. Conclusions NK cells play a role in promoting intra-abdominal adipose tissue macrophage infiltration and systemic insulin resistance in obesity. [ABSTRACT FROM AUTHOR]

Obesity is a major health crisis, and diabetes is one of its most serious sequelae. Obesity is associated with a state of chronic systemic inflammation that is a primary etiologic factor in the development of insulin resistance and diabetes. This inflammatory state is based in adipose tissue and mediated in large part by tissue macrophages and their cytokine and adipokine products. Recent research has identified specific molecular mediators of the link between inflammation and insulin resistance in obesity. Study of these mediators and the specific mechanisms underlying inflammation and insulin resistance in obesity holds the promise for novel pharmacotherapy for obesity-related metabolic disease. [ABSTRACT FROM AUTHOR]

Administrative and financial pressures on surgical education have created a need for efficient training curricula. Predictors of innate technical ability, which would guide the optimization of such a curriculum, are not well described. The goal of this study was to identify student characteristics predictive of innate pretraining skill level and response to training during the course of a four-week laparoscopic skills development program. Laparoscopic skills in 35 first-year surgical residents were assessed with the McGill Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS) before and after a four-week skills training program and after an interval of approximately 1 year. The correlation between trainee characteristics, including age, sex, designated surgical specialty, and laparoscopic skill level was assessed by using Pearson’s correlation and paired t-test studies. Intake MISTELS scores showed no significant correlation to age, sex, or designated field. Interns designated for the general surgery training program had significantly higher final scores than those entering other fields ( p = 0.02). There was a negative correlation between trainee age and both degree of improvement during training and final scores ( p = 0.02 and 0.05). A history of video game use correlated with significantly higher initial scores and better skills retention ( p = 0.03 and 0.04). A laparoscopic technical curriculum can achieve basic proficiency even when taught to a diverse group of trainees. Older residents beginning their surgical careers may be slower to develop technical skills. Choice of subspecialty seems to predict higher level of proficiency after completion of a skills training program among resident students. [ABSTRACT FROM AUTHOR]

Flow cytometry crossmatching (FCXM) was developed as a more sensitive assay than the standard complement-dependent cytotoxicity crossmatch (CDCXM) for the detection of anti-donor antibodies, that mediate hyperacute rejection and graft loss in the early post-transplant period in renal transplant recipients. The role of FCXM in predicting long-term clinical outcome in renal allograft recipients is unclear. This study examines the role of FCXM in predicting long-term clinical outcome in highly sensitized recipients of cadaveric renal transplants. All patients (n=100) with peak panel reactive antibody (PRA) levels>30%, who received cadaveric renal transplants between 1/1/’90 and 12/31/’95 at our institution, were divided into FCXM+ and FCXM- groups. The incidence of acute rejection was determined for each group during the first yr after transplant. Graft survival rates at 1, 2, and 3 yr, and creatinine levels were also compared between groups. FCXM+ patients experienced a higher incidence of acute rejection during the first yr after transplant (69 vs. 45%), and a higher percentage of FCXM+ patients had more than one episode of acute rejection during the first yr after transplant (34 vs. 8%) when compared to FCXM- patients. There was no statistically significant difference in 1-, 2-, or 3-yr graft survival between FCXM+ and FCXM- patients (76 vs. 83, 62 vs. 80, 62 vs. 72%, respectively). These results suggest that sensitized FCXM+ cadaveric renal transplant recipients have a higher incidence of acute rejection episodes in the first yr after transplant. Given the association of multiple rejection episodes with poor long-term allograft survival, FCXM may be a useful predictor of long-term clinical outcome in this sub-group of renal transplant recipients. [ABSTRACT FROM AUTHOR]

A case is presented in which an implantable cardioverter defibrillator (ICD) became infected in the abdominal wall pocket 5 weeks following implantation. There was no evidence clinically or by computed tomographic scan suggesting mediastinal extension of the infection. The infection was treated successfully by debriding the abdominal wall pocket followed by a combination of pocket irrigation with antibiotic solution, parenteral antibiotics, and long-term oral antibiotics. This conservative therapy was successful and avoided removal of the device. [ABSTRACT FROM AUTHOR]