Gastrointestinal stasis during sepsis may be associated with gastrointestinal smooth muscle dysfunction. Endotoxin [lipopolysaccharide (LPS)] impairs smooth muscle contraction, in part through inducible nitric oxide synthase (NOS II) and enhanced nitric oxide production. We studied the roles of tumor necrosis factor-α (TNF) and interleukin-1 (IL-1) in this process by using TNF binding protein (TNFbp) and IL-1 receptor antagonist (IL-1ra). Rats were treated with TNFbp and IL-1ra, or their vehicles, 1 h before receiving LPS or saline. At 5 h after LPS, contractility was measured in strips of ileal longitudinal smooth muscle, and NOS II activity was measured in full-thickness segments of ileum. LPS decreased maximum stress (mean ± SE) from 508 ± 55 (control) to 355 ± 33 g/cm2( P < 0.05). Pretreatment with TNFbp plus IL-1ra prevented the LPS-induced decrease. Separate studies of TNFbp alone or IL-1ra alone indicated that, at the doses and timing used, TNFbp was more effective. LPS also increased NOS II activity by >10-fold ( P < 0.01) over control. This increase was prevented by TNFbp plus IL-1ra ( P = not significant vs. control). We conclude that the LPS-induced increase in NOS II activity and the decrease in ileal muscle contractility are mediated by TNF and IL-1.
Background
Bariatric surgery reverses obesity-related comorbidities, including type 2 diabetes mellitus. Several studies have already described differences in anthropometrics and body composition between Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding patients, but the role of adipokines in the outcomes after the different types of surgery is not known.
Hypothesis
Differences in weight loss and reversal of insulin resistance exist between the two groups and correlate with changes in adipokines.
Methods
Fifteen severely obese women (mean BMI: 46.7 kg/m2) underwent two types of laparoscopic weight loss surgery (Roux-en-Y gastric bypass = 10, adjustable gastric banding = 5). Weight, waist and hip circumference, body composition, plasma metabolic markers, and lipids were measured at set intervals during a 24-month period after surgery.
Results
At 24 months, Roux-en-Y patients were overweight (BMI 29.7 kg/m2) while gastric banding patients remained obese (BMI 36.3 kg/m2). Roux-en-Y patients lost significantly more fat mass than gastric banding patients (mean difference 16.8 kg, p < 0.05). Likewise, leptin levels were lower in the Roux-en-Y patients (p = 0.003) and levels correlated with weight loss, loss of fat mass, insulin levels, and Homeostasis Model of Assessment 2 (HOMA-IR). Adiponectin correlated with insulin levels and HOMA-IR (r = −0.653, p = 0.04 and r = −0.674, p = 0.032, respectively) in the Roux-en-Y patients at 24 months.
Conclusions
After two years weight loss and normalization of metabolic parameters were less pronounced in patients who underwent gastric banding compared to patients who underwent Roux-en-Y gastric bypass. Our findings require confirmation in a prospective randomized trial.
Objective-To define muscle metabolic and cardiovascular changes following surgical intervention in clinically severe obese patients.Background-Obesity is a state of metabolic dysregulation which may lead to maladaptive changes in heart and skeletal muscle, including insulin resistance and heart failure. In a prospective longitudinal study 43 consecutive patients were subjected to metabolic profiling, skeletal muscle biopsies and resting echocardiograms at baseline as well as three and nine months after bariatric surgery.
This study was designed to determine if an increase in nitric oxide synthase (NOS) activity induced by lipopolysaccharide (LPS) is associated with increases in NOS II protein and mRNA abundance and with altered ileal longitudinal muscle contractility. Strips of muscle taken from LPS-treated, but not control, animals exhibited reduced in vitro contractility when L-arginine was a component of the physiological salt solution. This reduction was reversed by N omega-nitro-L-arginine (L-NNA), a competitive inhibitor of NOS. Full-thickness segments of jejunum, ileum, and colon taken 5 h after LPS injection exhibited increased NOS activity, NOS II immunoreactivity, and NOS II mRNA abundance. Increased NOS II immunoreactivity and mRNA abundance also were detected in ileal muscle strips taken from LPS-treated animals. These data confirm the reported effects of LPS on intestinal NOS activity and indicate that it can be attributed, at least in part, to an increase in NOS II mRNA and protein abundance. Furthermore, the data suggest that an LPS-induced increase in NOS II may lead to a decrease in ileal muscle contractility.
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