Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved.

Inflammatory bowel diseases (IBD), represented by ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic inflammation of the gastrointestinal tract, what leads to diarrhea, malnutrition, and weight loss. Depression of the growth hormone-insulin-like growth factor-1 axis (GH-IGF-1 axis) could be responsible of these symptoms. We demonstrate that long-term treatment (54 weeks) of adult CD patients with adalimumab (ADA) results in a decrease in serum IGF-1 without changes in serum IGF-1 binding protein (IGF1BP4). These results prompted us to conduct a preclinical study to test the efficiency of IGF-1 in the medication for experimental colitis. IGF-1 treatment of rats with DSS-induced colitis has a beneficial effect on the following circulating biochemical parameters: glucose, albumin, and total protein levels. In this experimental group we also observed healthy maintenance of colon size, body weight, and lean mass in comparison with the DSS-only group. Histological analysis revealed restoration of the mucosal barrier with the IGF-1 treatment, which was characterized by healthy quantities of mucin production, structural maintenance of adherers junctions (AJs), recuperation of E-cadherin and ß-catenin levels and decrease in infiltrating immune cells and in metalloproteinase-2 levels. The experimentally induced colitis caused activation of apoptosis markers, including cleaved caspase 3, caspase 8, and PARP and decreases cell-cycle checkpoint activators including phosphorylated Rb, cyclin E, and E2F1. The IGF-1 treatment inhibited cyclin E depletion and partially protects PARP levels. The beneficial effects of IGF-1 in experimental colitis could be explained by a re-sensitization of the IGF-1/IRS-1/AKT cascade to exogenous IGF-1. Given these results, we postulate that IGF-1 treatment of IBD patients could prove to be successful in reducing disease pathology.

The effects of truncal adiposity in forced spirometry: Sex differences.

The aim of the current paper is to establish the influence of truncal fat accumulation on the spirometric results of a group of healthy individuals. A cross-sectional study of 305 healthy, non-smoking adult subjects (144 males, 161 females) was conducted. Forced spirometry and dual-energy X-ray absorptiometry to quantify body fat were performed. Partial correlation and multiple linear regression analyses were performed. In females, abdominal fat was negatively correlated with forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). In males, thoracic fat was negatively correlated with respiratory variables, as was abdominal fat. In the multiple linear regression, FEV1 was the spirometric parameter that showed higher R2 values in both sexes. Truncal fat had a greater influence on FEV1 than on FVC. In males, no significant differences between the influence of thoracic and abdominal fat on spirometric results were found, and total body fat was shown to have more influence than regional. In females, the influence of abdominal fat was higher.