The adipokine orosomucoid alleviates adipose tissue fibrosis via the AMPK pathway.

The excess deposition of underlying extracellular matrix (ECM) in adipose tissue is defined as adipose tissue fibrosis that is a major contributor to metabolic disorder such as obesity and type 2 diabetes. Anti-fibrosis therapy has received much attention in the treatment of metabolic disorders. Orosomucoid (ORM) is an acute-phase protein mainly produced by liver, which is also an adipokine. In this study, we investigated the effects of ORM on adipose tissue fibrosis and the potential mechanisms. We showed that ORM1-deficient mice exhibited an obese phenotype, manifested by excessive collagen deposition in adipose tissues and elevated expression of ECM regulators such as metalloproteinases (MMP-2, MMP-13, MMP-14) and tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, TIMP-3). Administration of exogenous ORM (50 mg· kg-1· d-1, ip) for 7 consecutive days in high-fat diet (HFD)-fed mice and leptin receptor (LepR)-deficient db/db mice attenuated these abnormal expressions. Meanwhile, ORM administration stimulated AMP-activated protein kinase (AMPK) phosphorylation and decreased transforming growth factor-ß1 (TGF-ß1) level in adipose tissues of the mice. In TGF-ß1-treated 3T3-L1 fibroblasts, ORM (10 µg/mL) improved the impaired expression profiles of fibrosis-related genes, whereas a selective AMPK inhibitor dorsomorphin (1 µmol/mL) abolished these effects. Together, our results suggest that ORM exerts a direct anti-fibrosis effect in adipose tissue via AMPK activation. ORM is expected to become a novel target for the treatment of adipose tissue fibrosis.

α1-Acid Glycoprotein and Dietary Intake in End-Stage Renal Disease Patients.

Management of end-stage renal disease (ESRD) patients requires monitoring each of the components of malnutrition-inflammation-atherosclerosis (MIA) syndrome. Restrictive diet can negatively affect nutritional status and inflammation. An acute-phase protein-α1-acid glycoprotein (AGP), has been associated with energy metabolism in animal and human studies. The aim of our study was to look for a relationship between serum AGP concentrations, laboratory parameters, and nutrient intake in ESRD patients. The study included 59 patients treated with maintenance hemodialysis. A 24 h recall assessed dietary intake during four non-consecutive days-two days in the post-summer period, and two post-winter. Selected laboratory tests were performed: complete blood count, serum iron, total iron biding capacity (TIBC) and unsaturated iron biding capacity (UIBC), vitamin D, AGP, C-reactive protein (CRP), albumin, prealbumin, and phosphate-calcium metabolism markers (intact parathyroid hormone, calcium, phosphate). Recorded dietary intake was highly deficient. A majority of patients did not meet recommended daily requirements for energy, protein, fiber, iron, magnesium, folate, and vitamin D. AGP correlated positively with CRP (R = 0.66), platelets (R = 0.29), and negatively with iron (R = -0.27) and TIBC (R = -0.30). AGP correlated negatively with the dietary intake of plant protein (R = -0.40), potassium (R = -0.27), copper (R = -0.30), vitamin B6 (R = -0.27), and folates (R = -0.27), p < 0.05. However, in multiple regression adjusted for confounders, only CRP was significantly associated with AGP. Our results indicate that in hemodialyzed patients, serum AGP is weakly associated with dietary intake of several nutrients, including plant protein.

Albumin and transthyretin as risk factors for cataract: the POLA study.

OBJECTIVE: To assess the associations of markers of protein nutrition (plasma albumin and transthyretin) with cataract. METHODS: The Pathologies Oculaires Liées à l'Age (POLA) Study (1995-1997) is a population-based study on age-related eye diseases, performed in 2584 residents of Sète (South of France), aged 60 to 95 years. Cataract classification was based on a standardized lens examination at slitlamp according to Lens Opacities Classification System III. RESULTS: After multivariate adjustment, the risk for cataract (any type) was increased by about 50% in the lowest quintile of plasma albumin concentration (<38.28 g/L) and transthyretin concentration (<0.21 g/L) (odds ratio [OR], 1.49 [95% confidence interval (CI), 1.04-2.14]) and OR, 1.48 [95% CI, 1.03-2.13], respectively). The associations were stronger with mixed cataract (OR, 1.87 [95% CI, 0.95-3.68] and OR, 2.37 [95% CI, 1.22-4.59] for albumin and transthyretin levels, respectively) and nuclear cataract (OR, 2.39 [95% CI, 1.20-4.76] for low transthyretin levels). There were no significant associations with the other types of cataract. There were no associations of cataracts with high-sensitivity C-reactive protein and orosomucoid levels. CONCLUSIONS: This study is suggestive of an association of protein undernutrition with increased risk of cataract. Low protein intake may induce deficiencies of specific amino acids that are needed to maintain the health of the lens, or other nutritional deficiencies, particularly niacin, thiamin, and riboflavin.

Binding and displacement of basic, acidic and neutral drugs in normal and orosomucoid-deficient plasma.

The binding of the basic drugs quinidine, propranolol and amitriptyline, the neutral drug digitoxin and the acidic drug phenytoin to heparinised normal plasma, to orosomucoid (alpha 1-acid glycoprotein)-deficient plasma and to purified orosomucoid and albumin was studied in both the presence and absence of tris (2-butoxyethyl)-phosphate (TBEP) and de-(2-ethylhexyl)-phthalate (DEHP). The addition of TBEP and DEHP to heparinised plasma in concentrations up to 2.5 mmol/L markedly increased the unbound fractions of quinidine and propranolol, but the increase was less for amitiriptyline, TBEP being the most potent displacer. In orosomucoid-deficient plasma, which was prepared by immunoprecipitation, the free fraction of quinidine was similar to that of normal plasma in which maximal displacement with TBEP was obtained. The addition of the displacers to orosomucoid-deficient plasma caused no further reduction in the binding, nor was the plasma binding of digitoxin and phenytoin significantly affected. When combining purified albumin and orosomucoid in concentrations found in normal plasma, quinidine binding approached that of heparinised normal plasma. This study confirms the dominant role of orosomucoid in the variable plasma binding of basic drugs, and underlines the value of using immunologically prepared orosomucoid-deficient plasma and TBEP or DEHP as model displacers.