Objective-Experimental studies suggest that adipose inflammation is etiologically linked to obesity-induced systemic disease. Our goal was to characterize the state of inflammation in human fat in relation to vascular function and metabolic parameters in obese individuals. Methods and Results-We collected subcutaneous abdominal fat in 77 obese subjects (BMI Ն30 kg/m 2 ) and quantified adipose macrophage population using targeted immunohistochemistry. Brachial artery vasodilator function was examined using high-resolution vascular ultrasound. In 50 subjects, an inflamed adipose phenotype characterized by tissue macrophage accumulation in crown-like structures was associated with systemic hyperinsulinemia and insulin resistance (HOMA-IR 5.5Ϯ4.5 versus 2.6Ϯ1.9, Pϭ0.002) and impaired endothelium-dependent flow-mediated vasodilation (8.5Ϯ4.4% versus 10.8Ϯ3.8%, PϽ0.05), as compared to subjects with quiescent noninflamed adipose architecture (nϭ27). Macrophage retention in fat was linked to upregulated tissue CD68 and tumor necrosis factor (TNF)-␣ mRNA expression in addition to increased plasma hs-CRP. Conclusions-In a cohort of obese subjects, we demonstrate that proinflammatory changes in adipose tissue are associated with systemic arterial dysfunction and insulin resistance. These findings suggest that adipose inflammation may be linked to vascular injury and increased cardiovascular risk in obese subjects. (Arterioscler Thromb Vasc Biol. 2008;28:1654-1659)Key Words: obesity Ⅲ endothelium Ⅲ inflammation Ⅲ insulin Ⅲ vasculature O besity represents a disease state characterized by chronic subclinical inflammation linked to increased risk of type-2 diabetes and atherosclerosis. 1,2 Although the stimulus or source for persistent immune activation remains unclear, fat tissue is increasingly being recognized as an important hotbed of metabolic activity and a significant source of proatherogenic and proinflammatory adipocytokines that orchestrate metabolic and vascular dysfunction. 3,4 Animal studies suggest that adipose tissue macrophage (ATM) activity is functionally intertwined with systemic disease mechanisms. [5][6][7] The pathogenic link is supported by pharmacogenetic studies demonstrating that attenuation of ATM influx alters cytokine production and improves insulin sensitivity. 8,9 From a clinical perspective, inflammatory changes in fat have not been commonly investigated in human disease nor examined in the context of functional cardiovascular abnormalities.Inflammatory mechanisms are critical to all stages of cardiovascular disease progression and play a causal role in vascular endothelial dysfunction that represents a crucial early event in atherosclerosis and subsequent coronary heart disease (CHD) events. 10,11 These mechanisms are, in part, supported by local and systemic release of inflammatory cytokines that mediate activation of neutrophils, monocytes, and T-cells, promote lipid-laden foam cell accumulation, weaken atherosclerotic plaque stability, and impair nitric oxide (NO)-mediated endothelium-depend...

Hypothesis: There is an increase in the amount of time required to perform an operation when the procedure involves training a surgical resident. This increased time does not translate into a financial burden for the hospital. Design: Retrospective review of prospectively collected data. During the study period, surgeons and residents were blinded to the study's intent. We compared the operative times of academic surgeons performing 4 common surgical procedures before and after the introduction of a postgraduate year 3 resident into a community teaching hospital. Between January 1, 2001, and June 30, 2002, 4 academic surgeons performed operations without a resident in a community hospital that was recently integrated into a tertiary medical center system. During that period, surgeons operated alone (hernia surgery) or assisted one another (laparoscopic cholecystectomy, colectomy, and carotid endarterectomy). From July 1, 2002, through March 31, 2003, these same 4 surgeons were assisted by a postgraduate year 3 resident on similar procedures. Setting: Community hospital recently integrated into a tertiary medical center system. Participants: Four experienced academic surgeons operating in the community setting and patients undergoing 1 of 4 surgical procedures (inguinal hernia repair, laparoscopic cholecystectomy, partial colectomy, or carotid endarterectomy) from January 1, 2001, through March 31, 2003. Intervention: The introduction of a postgraduate year 3 surgical resident rotation into a community hospital in which the same academic surgeons had been performing operations without a resident for 18 months. Main Outcome Measures: Mean operating time with and without a postgraduate year 3 resident participating in 4 common surgical procedures. Result: For the 4 procedures studied, there was a significant increase in the operative time required to complete such procedures. Conclusions: There is an increased time cost associated with the operative training of surgical residents. This "cost" primarily impacts the attending surgeon.

Abbreviations: AMPK, AMP kinase; BMI, body mass index; HOMA-IR, homeostatic model assessment of insulin resistance.

Objective The purpose of this study was to characterize the relationship between adipose tissue phenotype and depot-specific microvascular function in fat. Methods and Results In 30 obese subjects (age 42±11 yr, BMI 46±11 kg/m2) undergoing bariatric surgery, we intra-operatively collected visceral and subcutaneous adipose tissue and characterized depot-specific adipose phenotypes. We assessed vasomotor function of the adipose microvasculature using videomicroscopy of small arterioles (75–250 μm) isolated from different fat compartments. Endothelium-dependent, acetylcholine-mediated vasodilation was severely impaired in visceral arterioles, compared to the subcutaneous depot (P<0.001 by ANOVA). Non-endothelium dependent responses to papaverine and nitroprusside were similar. Endothelial nitric oxide synthase (eNOS) inhibition with Nω-nitro-L-arginine methyl ester (L-NAME) reduced subcutaneous vasodilation but had no effect on severely blunted visceral arteriolar responses. Visceral fat exhibited greater expression of proinflammatory, oxidative stress-related, hypoxia-induced, and proangiogenic genes; increased activated macrophage populations; and higher capacity for cytokine production ex vivo. Conclusions Our findings provide clinical evidence that the visceral microenvironment may be intrinsically toxic to arterial health providing a potential mechanism by which visceral adiposity burden is linked to atherosclerotic vascular disease. Our findings also support the evolving concept that both adipose tissue quality and quantity may play significant roles in shaping cardiovascular phenotypes in human obesity.