Energy Metabolism in Japanese Patients with Crohn’s Disease

We investigated energy expenditure in hospitalized patients with Crohn’s disease (CD), and determined optimal energy requirements for nutritional therapy. Sixteen patients (5 women and 11 men, mean age 36 year old, mean BMI 18.7 kg/m2) and 8 healthy volunteers were enrolled in this study. Measured resting energy expenditure (mREE) levels were determined by indirect calorimetry. The mREEs in CD patients were significantly higher than those of healthy controls (24.4 ± 2.4 kcal/kg/day vs 21.3 ± 1.7 kcal/kg/day). However, mREEs in CD patients were significantly lower than predicted REEs (pREEs) calculated by the Harris-Benedict equation (26.4 ± 2.5 kcal/kg/day). Furthermore, mREE/pREE values were lower in undernourished patients than in well-nourished patients. CD patients had hyper-metabolic statuses evaluated by mREE/body weight, but increased energy expenditure did not contribute to weight loss in these patients. In conclusion, nutritional therapy with 25–30 kcal/ideal body weight/day (calculated by mREE × active factor) may be optimal for active CD patients, while higher energy intake values pose the risk of overfeeding

Serum Concentrations of Trace Elements in Patients with Crohn’s Disease Receiving Enteral Nutrition

We investigated the trace element status in Crohn’s disease (CD) patients receiving enteral nutrition, and evaluated the effects of trace element-rich supplementation. Thirty-one patients with CD were enrolled in this study. All patients were placed on an enteral nutrition regimen with Elental® (Ajinomoto pharmaceutical. Ltd., Tokyo, Japan). Serum selenium, zinc and copper concentrations were determined by atomic absorption spectroscopy. Serum selenoprotein P levels were determined by an ELISA system. Average serum levels of albumin, selenium, zinc and copper were 4.1 ± 0.4 g/dl, 11.2 ± 2.8 µg/dl, 71.0 ± 14.8 µg/dl, and 112.0 ± 25.6 µg/dl, respectively. In 9 patients of 31 CD patients, serum albumin levels were lower than the lower limit of the normal range. Serum selenium, zinc and copper levels were lower than lower limits in 12 patients, 9 patients and 1 patient, respectively. Serum selenium levels significantly correlated with both serum selenoprotein P levels and glutathione peroxidase activity. Supplementation of selenium (100 µg/day) and zinc (10 mg/day) for 2 months significantly improved the trace element status in CD patients. In conclusion, serum selenium and zinc levels are lower in many CD patients on long-term enteral nutrition. In these patients, supplementation of selenium and zinc was effective in improving the trace element status

Energy Expenditure in Japanese Patients with Severe or Moderate Ulcerative Colitis

We investigated the energy expenditure in hospitalized patients with severe or moderate ulcerative colitis (UC), and compared them to healthy controls. Thirteen patients (5 women and 8 men; mean age 31.8 years; mean BMI 19.0 kg/m2) and 10 healthy volunteers were enrolled in this study. The resting energy expenditure (mREE) levels were determined by indirect calorimetry. The mREEs of the UC patients were significantly higher than those of healthy controls (26.4 ± 3.6 vs 21.8 ± 1.7 kcal/kg/day), although the mREEs of the UC patients were almost the same as the predicted REEs (pREEs) calculated by the Harris-Benedict equation (26.4 ± 2.4 kcal/kg/day vs 26.5 ± 2.6 kcal/kg/day). The mREE/pREE ratio, which reflects stress, was 1.0 ± 0.15. In the UC patients, a significant correlation was observed between the mREEs and the clinical activity index. In conclusion, UC patients showed a hyper-metabolic status as evaluated by their mREE/body weight. Energy expenditure was significantly correlated with disease activity. From our observations, we recommend that nutritional management with more than 30–35 kcal/ideal body weight/day (calculated by the mREE × activity factor) may be optimal for active severe or moderate ulcerative colitis

Regulatory Role of GRK2 in the TLR Signaling-Mediated iNOS Induction Pathway in Microglial Cells

G protein-coupled receptor kinase 2 (GRK2) is a ubiquitous member of the GRK family that restrains cellular activation by G protein-coupled receptor (GPCR) phosphorylation leading to receptor desensitization and internalization, but has been identified to regulate a variety of signaling molecules, among which may be associated with inflammation. In this study, we attempted to establish the regulatory role of GRK2 in the Toll-like receptor (TLR) signaling pathway for inducible nitric oxide synthase (iNOS) expression in microglial cells. When mouse MG6 cells were stimulated with the TLR4 ligands lipopolysaccharide (LPS) and paclitaxel, we found that interferon regulatory factor 1 (IRF1) protein expression and activation was upregulated, transcription of interferon-β (IFN-β) was accelerated, induction/activation of STAT1 and activation of STAT3 were promoted, and subsequently iNOS expression was upregulated. The ablation of GRK2 by small interfering RNAs (siRNAs) not only eliminated TLR4-mediated upregulation of IRF1 protein expression and nuclear translocation but also suppressed the activation of the STAT pathway, resulting in negating the iNOS upregulation. The TLR3-mediated changes in IRF1 and STAT1/3, leading to iNOS induction, were also abrogated by siRNA knockdown of GRK2. Furthermore, transfection of GRK2 siRNA blocked the exogenous IFN-β supplementation-induced increases in phosphorylation of STAT1 as well as STAT3 and abrogated the augmentation of iNOS expression in the presence of exogenous IFN-β. Taken together, our results show that GRK2 regulates the activation of IRF1 as well as the activation of the STAT pathway, leading to upregulated transcription of iNOS in activated microglial cells. Modulation of the TLR signaling pathway via GRK2 in microglia may be a novel therapeutic target for treatment of neuroinflammatory disorders