Components of the adipose tissue (AT) extracellular matrix (ECM) are recently discovered contributors to obesity-related cardiometabolic disease. We identified increased adipocyte expression of ECM-related clusterin (apolipoprotein J) in obese versus lean women by microarray. Our objective was to determine 1) whether subcutaneous AT adipocyte (SAd) clusterin and serum clusterin are associated with insulin resistance (IR) and known markers of cardiometabolic risk and 2) how clusterin may contribute to increased risk. RESEARCH DESIGN AND METHODS We validated increased clusterin expression in adipocytes from a separate group of 18 lean and 54 obese individuals. The relationship of clusterin gene expression and plasma clusterin with IR, cardiovascular biomarkers, and risk of cardiovascular disease (CVD) was then determined. Further investigations in human cultured cells and in aged LDLR 2/2 mice prone to development of obesityassociated complications were performed. RESULTS SAd clusterin correlated with IR, multiple CVD biomarkers, and CVD risk, independent of traditional risk factors. Circulating human clusterin exhibited similar associations. In human adipocytes, palmitate enhanced clusterin secretion, and in human hepatocytes, clusterin attenuated insulin signaling and APOA1 expression and stimulated hepatic gluconeogenesis. LRP2 (megalin), a clusterin receptor, highly expressed in liver, mediated these effects, which were inhibited by LRP2 siRNA. In response to Western diet feeding, an increase in adipocyte clusterin expression was associated with a progressive increase in liver fat, steatohepatitis, and fibrosis in aged LDLR 2/2 mice. CONCLUSIONS Adipocyte-derived clusterin is a novel ECM-related protein linking cardiometabolic disease and obesity through its actions in the liver. Obesity is associated with a heightened cardiovascular disease (CVD) risk profile that encompasses insulin resistance (IR), type 2 diabetes, hypertension, dyslipidemia, and hepatic steatosisdall components of the well-described metabolic syndrome (1,2). These factors act synergistically to accelerate morbidity and mortality in obesity (3). IR stems from adipocyte lipolysis and lipid deposition into insulin target tissues, as well
Decreased adipose tissue regulatory T cells contribute to insulin resistance in obese mice, however, little is known about the mechanisms regulating adipose tissue regulatory T cells numbers in humans. Here we obtain adipose tissue from obese and lean volunteers. Regulatory T cell abundance is lower in obese vs. lean visceral and subcutaneous adipose tissue and associates with reduced insulin sensitivity and altered adipocyte metabolic gene expression. Regulatory T cells numbers decline following high-fat diet induction in lean volunteers. We see alteration in major histocompatibility complex II pathway in adipocytes from obese patients and after high fat ingestion, which increases T helper 1 cell numbers and decreases regulatory T cell differentiation. We also observe increased expression of inhibitory co-receptors including programmed cell death protein 1 and OX40 in visceral adipose tissue regulatory T cells from patients with obesity. In human obesity, these global effects of interferon gamma to reduce regulatory T cells and diminish their function appear to instigate adipose inflammation and suppress adipocyte metabolism, leading to insulin resistance.
Background COVID-19 has created an urgent need for reorganization and surge planning among departments of surgery across the USA. Methods Review of the COVID-19 planning process and work products in preparation for a patient surge. Organizational and process changes, workflow redesign, and communication plans are presented. Results The planning process included widespread collaboration among leadership from many disciplines. The department of surgery played a leading role in establishing clinical protocols, guidelines, and policies in preparation for a surge of COVID-19 patients. A multidisciplinary approach with input from clinical and nonclinical stakeholders is critical to successful crisis planning. A clear communication plan should be implemented early and input from trainees, staff, and faculty should be solicited. Conclusion Major departmental and health system reorganization is required to adapt academic surgical practices to a widespread crisis. Surgical leadership, innovation, and flexibility are critical to successful planning and implementation.
COVID-19 is a pandemic which has affected almost every aspect of our life since starting globally in November 2019. Given the rapidity of spread and inadequate time to prepare for record numbers of sick patients, our surgical community faces an unforeseen challenge. SAGES is committed to the protection and care of patients, their surgeons and staff, and all who are served by the medical community at large. This includes physical health, mental health, and well-being of all involved. The fear of the unknown ahead can be paralyzing. International news media have chronicled the unthinkable situations that physicians and other health care providers have been thrust into as a result of the COVID-19 pandemic. These situations include making life or death decisions for patients and their families regarding use of limited health care resources. It includes caring for patients with quickly deteriorating conditions and limited treatments available. Until recently, these situations seemed far from home, and now they are in our own hospitals. As the pandemic broadened its reach, the reality that we as surgeons may be joining the front line is real. It may be happening to you now; it may be on the horizon in the coming weeks. In this context, SAGES put together this document addressing concerns on clinician stressors in these times of uncertainty. We chose to focus on the emotional toll of the situation on the clinician, protecting vulnerable persons, reckoning with social isolation, and promoting wellness during this crisis. At the same time, the last part of this document deals with the "light at the end of the tunnel," discussing potential opportunities, lessons learned, and the positives that can come out of this crisis. Keywords Surgeon wellness • COVID-19 • Pandemic well-being • Burnout COVID-19 is a pandemic which has affected almost every aspect of our life since starting globally in November 2019. Given the rapidity of spread and inadequate time to prepare for record numbers of sick patients, our surgical community faces an unforeseen challenge. SAGES is committed to the protection and care of patients, their surgeons and staff, and all who are served by the medical community at large. This
Obesity is associated with a state of chronic low-grade inflammation both systemically and within specific tissues, including adipose tissue (AT). In murine models of obesity, there is a shift in the inflammatory profile of the AT immune cells, with an accumulation of proinflammatory M1 macrophages that surround the expanding adipocyte. However, much less is known about the immune cell composition and how to best define AT macrophages in humans. Objective. The goals of the current study were to determine the contribution of macrophages to the stromal vascular fraction (SVF) in lean versus obese human visceral AT (VAT); examine the expression of common M1, M2, and pan macrophage markers; and determine the association of specific macrophage types with known biomarkers of obesity-related cardiometabolic disease. Research Design and Methods. VAT biopsies were obtained from obese (n = 50) and lean (n = 8) patients during elective surgery. Adipocytes and SVF were isolated, and the SVF was subjected to flow cytometry analyses. Results. Our results indicate that VAT macrophages are increased in obesity and associate with biomarkers of CVD but that many macrophages do not fall into currently defined M1/M2 classification system based on CD206 receptor expression levels. Conclusions. VAT macrophages are increased in obese subjects, but the current markers used to define macrophage populations are inadequate to distinguish differences in human obesity. Further studies are needed to delineate the function of AT macrophages in the maintenance and progression of human AT inflammation in obesity.
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