Dietary fat promotes pathological insulin resistance through chronic inflammation1–3. Macrophage inactivation of inflammatory proteins improves diet-induced diabetes4, but how nutrient-dense diets induce diabetes is unknown5. Membrane lipids affect the innate immune response6, which requires domains7 that influence high-fat diet (HFD)-induced chronic inflammation8,9 and alter cell function based on phospholipid composition10. Endogenous fatty acid synthesis, mediated by fatty acid synthase (FAS)11, affects membrane composition. Here we show that macrophage FAS is indispensable for dietinduced inflammation. Deleting FAS in macrophages prevents diet-induced insulin resistance, adipose macrophage recruitment, and chronic inflammation in mice. FAS deficiency alters membrane order and composition, impairing retention of plasma membrane cholesterol, as well as disrupting Rho GTPase trafficking required for cell adhesion, migration, and activation. Expressing a constitutively active Rho GTPase restored inflammatory signaling. Exogenous palmitate partitioned to different pools than endogenous lipids and did not rescue inflammatory signaling. However, exogenous cholesterol as well as other planar sterols rescued signaling, and exogenous cholesterol restored FAS-induced perturbations in membrane order. Endogenous fat production in macrophages is necessary for exogenous fat-induced insulin resistance by creating a receptive environment at the plasma membrane for assembly of cholesterol-dependent signaling networks.

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Background: Overlapping surgery occurs when a single surgeon is the primary surgeon for >1 patient in separate operating rooms simultaneously. The surgeon is present for the critical portions of each patient's operation although not present for the entirety of the case. While overlapping surgery has been widely utilized across surgical subspecialties, few large studies have compared the safety of overlapping and nonoverlapping surgery. Methods: In this retrospective cohort study, we reviewed the charts of patients who had undergone orthopaedic surgery at our ambulatory surgery center during the period of April 2009 and October 2015. A database of operations, including patient and surgical characteristics, was compiled. Complications had been identified and logged into the database by surgeons monthly over the study period. These monthly reports and case logs were reviewed retrospectively to identify complications. Propensity-score weighting and logistic regression models were used to determine the association between outcomes and overlapping surgery. Results: A total of 22,220 operations were included. Of these, 5,198 (23%) were overlapping, and 17,022 (77%) were nonoverlapping. The median duration of surgery overlap was 8 minutes (quartile 1 to quartile 3, 3 to 16 minutes); no operations were concurrent. After weighting, the only continuous variables that differed significantly between the groups were operative time (median, 57 compared with 56 minutes for the overlapping and the nonoverlapping group, respectively; p = 0.022), anesthesia time (median, 97 compared with 93 minutes; p < 0.001), and total tourniquet time (median, 26 compared with 22 minutes; p = 0.0093). Multivariable logistic regression models did not demonstrate an association between overlapping surgery and surgical site infection, noninfection surgical complications, hospitalization, or morbidity. Conclusions: These data suggest that there is no association between briefly overlapping surgery and surgical site infection, noninfection surgical complications, hospitalization, and morbidity. When practiced in the manner described herein, overlapping orthopaedic surgery can be a safe practice in the ambulatory setting. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. O verlapping surgery occurs when a single surgeon is the primary surgeon for >1 patient in separate operating rooms simultaneously. The surgeon is present for the critical portions of each patient's operation although not present for the entirety of the case. Although overlapping surgery has only recently been recognized by the greater public, its use has been supported to hone trainee skills, increase access to highly sought-after surgeons, and improve cost-effectiveness 1-3. Additionally, prior work in multiple surgical subspecialties has shown that surgical resident involvement improves patient care by bringing additional knowledge and viewpoints, questions, and assistance during cases 4-10. However, common conce...