osteoprotegerin and Fatty-Liver

Studies have demonstrated that obesity and osteoporosis are linked disorders in humans. This study examined the hypothesis that excessive lipid consumption affects bone metabolism in laying hens. A total of one hundred 63-wk-old laying hens were randomly divided into 2 treatments and fed either a regular layer diet (control) or a high energy and low protein diet (HE-LP; experimental treatment) for 80 d. Egg production, feed intake, and BW were recorded at various days during the treatment. At d 80, ten randomly chosen birds per treatment group were killed. Abdominal fat weight, liver weight, and liver fat content were determined. Serum levels of total calcium, inorganic phosphate, and alkaline phosphatase were measured using a biochemical analyzer. Serum concentrations of osteocalcin, leptin-like protein, and estrogen were measured by enzyme-linked immunosorbent assay. Tibia length and width were measured using a vernier caliper; density of the right tibias was determined using an x-ray scanner; and mechanical properties of the left tibias were analyzed using a material testing machine. The expression of osteocalcin and osteoprotegerin mRNA in the keel bone was analyzed by real-time PCR. The concentration of osteocalcin protein in the keels was measured using western blot. Compared with control hens, hens fed the HE-LP diet had lower egg production, lower feed intake, greater liver fat content, and greater abdominal fat pad mass (P < 0.05). Feeding the HE-LP diet increased serum alkaline phosphatase activity, osteocalcin, leptin-like protein, and estrogen concentrations (P < 0.05), and decreased the keel osteocalcin concentrations (P < 0.05). There were significant positive correlations between the serum concentrations of leptin-like protein, estrogen, and osteocalcin regardless of treatment (P < 0.05). The results indicated that HE-LP diet induced a fatty liver disorder in laying hens with an upregulation in bone turnover and exacerbated skeletal damage. The data supported a role for lipid metabolism in skeletal heath of laying hens.

Topics: Animals; Biomarkers; Bone Remodeling; Chickens; Dietary Fats; Dietary Proteins; Fatty Liver; Female; Lipid Metabolism; Osteocalcin; Osteoprotegerin; Oviposition; Poultry Diseases; Real-Time Polymerase Chain Reaction; RNA, Messenger

Previous cross-sectional studies have established that circulating osteoprotegerin (OPG) levels are associated with nonalcoholic fatty liver disease (NAFLD). However, the role of OPG in metabolic diseases, such as diabetes and NAFLD, is still unclear. In the current study, we demonstrated that hepatic OPG expression was downregulated in NAFLD individuals and in obese mice. OPG deficiency decreased lipid accumulation and expression of CD36 and peroxisome proliferator-activated receptor-γ (PPAR-γ) in the livers of OPG

Topics: Animals; CD36 Antigens; Extracellular Signal-Regulated MAP Kinases; Fatty Liver; Hepatocytes; Humans; Liver; Mice; Mice, Knockout; Non-alcoholic Fatty Liver Disease; Obesity; Osteoprotegerin; Phosphorylation; PPAR gamma; Signal Transduction

Hepatic osteodystrophy is multifactorial in its pathogenesis. Numerous studies have shown that impairments of the hepatic growth hormone/insulin-like growth factor-1 axis (GH/IGF-1) are common in patients with non-alcoholic fatty liver disease, chronic viral hepatitis, liver cirrhosis, and chronic cholestatic liver disease. Moreover, these conditions are also associated with low bone mineral density (BMD) and greater fracture risk, particularly in cortical bone sites. Hence, we addressed whether disruptions in the GH/IGF-1 axis were causally related to the low bone mass in states of chronic liver disease using a mouse model of liver-specific GH-receptor (GHR) gene deletion (Li-GHRKO). These mice exhibit chronic hepatic steatosis, local inflammation, and reduced BMD. We then employed a crossing strategy to restore liver production of IGF-1 via hepatic IGF-1 transgene (HIT). The resultant Li-GHRKO-HIT mouse model allowed us to dissect the roles of liver-derived IGF-1 in the pathogenesis of osteodystrophy during liver disease. We found that hepatic IGF-1 restored cortical bone acquisition, microarchitecture, and mechanical properties during growth in Li-GHRKO-HIT mice, which was maintained during aging. However, trabecular bone volume was not restored in the Li-GHRKO-HIT mice. We found increased bone resorption indices in vivo as well as increased basal reactive oxygen species and increased mitochondrial stress in osteoblast cultures from Li-GHRKO and the Li-GHRKO-HIT compared with control mice. Changes in systemic markers such as inflammatory cytokines, osteoprotegerin, osteopontin, parathyroid hormone, osteocalcin, or carboxy-terminal collagen cross-links could not fully account for the diminished trabecular bone in the Li-GHRKO-HIT mice. Thus, the reduced serum IGF-1 associated with hepatic osteodystrophy is a main determinant of low cortical but not trabecular bone mass. © 2017 American Society for Bone and Mineral Research.

Topics: Animals; Biomechanical Phenomena; Bone Density; Bone Diseases, Metabolic; Cancellous Bone; Chronic Disease; Cortical Bone; Cytokines; Fatty Liver; Inflammation; Inflammation Mediators; Insulin-Like Growth Factor I; Liver; Mice, Inbred C57BL; Mice, Transgenic; Organ Size; Organ Specificity; Osteoblasts; Osteopontin; Osteoprotegerin; Receptors, Somatotropin; Transgenes; X-Ray Microtomography

This study aimed to determine the association between visceral adipose tissue (VAT), liver fat (LF) content, and other markers of the metabolic syndrome (MetS) and osteoprotegerin (OPG) in dysmetabolic adults.. Subjects from the NUMEVOX cohort were included if they fulfilled at least one MetS criterion. They then underwent a thorough metabolic and cardiovascular evaluation, including arterial stiffness, atherosclerotic plaques, homoeostasis model assessment for insulin resistance (HOMA-IR) indices and OPG. VAT and LF content were measured by magnetic resonance imaging (MRI). Ultrasound examination of arteries and arterial stiffness were recorded, and age- and gender-adjusted paired correlations calculated.. Body mass index, waist circumference and MRI-derived VAT correlated with OPG, whereas abdominal subcutaneous fat did not. OPG levels were strongly correlated with LF content (r=0.25, P=0.003), liver markers such as alanine aminotransferase (r=0.39, P<0.001) and HOMA-IR index (r=0.39, P<0.0001). Plasma OPG also correlated with arterial stiffness and the number of atherosclerotic sites.. Plasma OPG levels are positively associated with both liver markers and increased LF content, but not with subcutaneous fat in dysmetabolic men. These findings suggest that elevated OPG levels may play a role in the link between fatty liver disease and enhanced cardiovascular risk.

Topics: Adult; Biomarkers; Body Mass Index; Cohort Studies; Fatty Liver; Female; Humans; Insulin Resistance; Intra-Abdominal Fat; Liver; Male; Metabolic Syndrome; Middle Aged; Osteoprotegerin

Although liver biopsy remains the best diagnostic standard for nonalcoholic steatohepatitis (NASH), non-invasive tests are eagerly awaited. In this study, we sought to develop a support vector machine (SVM) algorithm to discriminate with high accuracy between subjects with NASH and controls using a blood-based biomarker panel.. A total of 17 biomarkers were measured by commercially available enzyme-linked immunosorbent assays in 136 serum samples from patients with biopsy-proven NASH (n = 60) and subjects with normal ALT and no evidence of fatty liver on ultrasound (n = 76). The database was randomly divided (1:1 fashion) into a discovery set for classification training and in a validation set of the chosen biomarkers in blinded samples. Multivariate analysis was performed by means of SVM.. After the identification of a group of three most discriminative biomarkers (osteoprotegerin, fibroblast growth factor 21, and M30) in the discovery set, the application of SVM to the validation test resulted in a 92.5% sensitivity and 84.1% specificity for distinguishing subjects with NASH from controls.. A targeted biomarker profiling combined with a SVM-based pattern identification approach may allow the identification of patients with NASH with clinically relevant accuracy and validity.

Topics: Biomarkers; Body Mass Index; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Fatty Liver; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Male; Middle Aged; Multivariate Analysis; Non-alcoholic Fatty Liver Disease; Osteoprotegerin; Sensitivity and Specificity

Osteoprotegerin (OPG) is a member of the tumor necrosis factor superfamily with pleiotropic effects on inflammation, endocrine function and the immune system. Reduced OPG levels are related to insulin resistance. We tested the hypothesis that serum levels of OPG may be associated with nonalcoholic fatty liver disease (NAFLD).. Four groups of patients were enrolled in the present study: subjects with definite nonalcoholic steatohepatitis (NASH, n = 56), borderline NASH (n = 26), simple fatty liver (n = 17) and healthy controls without evidence of liver disease (n = 58). Serum levels of OPG were measured by ELISA.. Concentrations of OPG were significantly lower in patients with definite NASH (median: 45 pg/mL, p < 0.001) and borderline NASH (57 pg/mL, p < 0.001) than in controls (92 pg/mL). The area under the ROC curve for distinguishing between steatohepatitis (definite NASH plus borderline NASH) and healthy controls using OPG was 0.82. The use of a cut-off level < 74 pg/mL for serum OPG levels yielded sensitivity and specificity values of 75.6% and 75.9%, respectively.. Serum osteoprotegerin concentrations are reduced in patients with the more severe forms of NAFLD and may serve as a noninvasive biomarker to identify patients with NASH.

Topics: Alcohols; Case-Control Studies; Diagnosis, Differential; Fatty Liver; Female; Humans; Male; Middle Aged; Osteoprotegerin; ROC Curve