Reduction Of Low-grade Inflammation Research Articles

TRPV1 Antagonists as Novel Anti-Diabetic Agents: Regulation of Oral Glucose Tolerance and Insulin Secretion Through Reduction of Low-Grade Inflammation?

With a global prevalence among adults over 18 years of age approaching 9%, Type 2 diabetes mellitus (T2DM) has reached pandemic proportions and represents a major unmet medical need. To date, no disease modifying treatment is available for T2DM patients. Accumulating evidence suggest that the sensory nervous system is involved in the progression of T2DM by maintaining low-grade inflammation via the vanilloid (capsaicin) receptor, Transient Receptor Potential Vanilloid-1 (TRPV1). In this study, we tested the hypothesis that TRPV1 is directly involved in glucose homeostasis in rodents. TRPV1 receptor knockout mice (Trpv1−/−) and their wild-type littermates were kept on high-fat diet for 15 weeks. Moreover, Zucker obese rats were given the small molecule TRPV1 antagonist, N-(4-Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine-1(2H)-carbox-amide (BCTC), per os twice-a-day or vehicle for eight days. Oral glucose tolerance and glucose-stimulated insulin secretion was improved by both genetic inactivation (Trpv1−/− mice) and pharmacological blockade (BCTC) of TRPV1. In the obese rat, the improved glucose tolerance was accompanied by a reduction in inflammatory markers in the mesenteric fat, suggesting that blockade of low-grade inflammation contributes to the positive effect of TRPV1 antagonism on glucose metabolism. We propose that TRPV1 could be a promising therapeutic target in T2DM by improving glucose intolerance and correcting dysfunctional insulin secretion.

Reduction of coagulability state one year after bariatric surgery

BackgroundObese patients are in a hypercoagulable state relative to normal-weight patients. Low-grade inflammation may be a key factor for this condition. ObjectivesOur study aimed to compare the coagulability state of morbidly obese patients before and 1 year after bariatric surgery (BS) using the Thrombin Generation (TG) test, a validated method to assess coagulation in vitro. SettingUniversity hospital. MethodsAll patients undergoing BS between September 1, 2014 and April 30, 2015 were eligible for this prospective study (n = 42). Two distinct reagents were used for TG initiation based on the tissue factor concentration (Reagents LOW and HIGH). The main outcomes were endogenous thrombin potential (ETP) and peak height of TG. The rate of follow-up after one year was 97%. ResultsOne year after surgery, %weight loss was 32.5±8.4%; CRP decreased from 9.0 (3.7–12.9) to 1.1 (0.3–2.8) mg/mL (P<.001) and fibrinogen from 4.2±.8 to 3.5±.8 g/L (P<.001). The ETP (%) decreased from (108.0 (95.0–117.0) to 78.0 (71.0–98.0) (P<.001) (LOW reagent) and from 113.0 (103.0–134.0) to 96.0 (86.0–107.0) (P<.001) (HIGH reagent). Peak height (%) decreased from (117.0 (92.0–139.0) to 82.0 (70.0–111.0) (P = .003) (LOW reagent) and from 106.0 (96.0–118.0) to 97.0 (87.8–105.2) (P = .003) (HIGH reagent). ConclusionOur study shows a significant reduction in TG potential one year after BS in morbidly obese patients. Reduction of low grade inflammation may be one of the underlying mechanisms.

Effect of antihypertensive treatment with lercanidipine on endothelial progenitor cells and inflammation in patients with mild to moderate essential hypertension

Background: It has been demonstrated that circulating endothelial progenitor cells (EPCs) number reflects the endogenous vascular repair ability, with the EPCs pool declining in presence of cardiovascular risk factors. Several drugs, including dihydropyridine calcium channel blockers, have been reported to elicit antioxidant and anti-inflammatory properties, as well as to improve vascular remodeling and dysfunction. However, no data are available about the effects of lercanidipine on EPCs. The aim of the present study was therefore to investigate the effects of short-term treatment with lercanidipine on circulating EPCs, as well as on indices of inflammation and oxidative stress.Patients and methods: Twenty essential hypertensive patients were included in the study and treated for 4 weeks with lercanidipine 20 mg per day orally. Investigations were performed in basal condition, after appropriate wash out of previous treatments, and after 4 weeks of lercanidipine treatment. Inflammatory and oxidative stress markers were assessed by ELISA technique. Lin-/7AAD-/CD34+/CD133+/VEGFR-2 + and Lin-/7AAD-/CD34+/VEGFR-2 + cells were identified by flow cytometry and considered as EPCs. EPCs cells were expressed as number of cells per million Lin-mononuclear cells.Results: Circulating EPCs were significantly increased after lercanidipine treatment (CD34+/CD133+/VEGFR-2 + cells: 78.3 ± 64.5 vs 46.6 ± 32.8; CD34+/VEGFR-2+: 87996 ± 165116 vs 1026 ± 1559, respectively, p < 0.05). A modest reduction in circulating indices of inflammation was also observed.Conclusions: In conclusion, lercanidipine is able to increase the number of circulating EPCs, possibly through a reduction of low-grade inflammation.

Reduction of low grade inflammation restores blunting of postprandial muscle anabolism and limits sarcopenia in old rats

Ageing is characterized by a decline in muscle mass that could be explained by a defect in the regulation of postprandial muscle protein metabolism. Indeed, the stimulatory effect of food intake on protein synthesis and its inhibitory effect on proteolysis is blunted in old muscles from both animals and humans. Recently, low grade inflammation has been suspected to be one of the factors responsible for the decreased sensitivity of muscle protein metabolism to food intake. This study was undertaken to examine the effect of long-term prevention of low grade inflammation on muscle protein metabolism during ageing. Old rats (20 months of age) were separated into two groups: a control group and a group (IBU) in which low grade inflammation had been reduced with a non-steroidal anti inflammatory drug (ibuprofen). After 5 months of treatment, inflammatory markers and cytokine levels were significantly improved in treated old rats when compared with the controls: -22.3% fibrinogen, -54.2% alpha2-macroglobulin, +12.6% albumin, -59.6% IL(6) and -45.9% IL(1beta) levels. As expected, food intake had no effect on muscle protein synthesis or muscle proteolysis in controls whereas it significantly increased muscle protein synthesis by 24.8% and significantly decreased proteolysis in IBU rats. The restoration of muscle protein anabolism at the postprandial state by controlling the development of low grade inflammation in old rats significantly decreased muscle mass loss between 20 and 25 months of age. In conclusion, the observations made in this study have identified low grade inflammation as an important target for pharmacological, nutritional and lifestyle interventions that aim to limit sarcopenia and muscle weakness in the rapidly growing elderly population in Europe and North America.