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https://www.readbyqxmd.com/read/27906582/fiat-deletion-increases-bone-mass-but-does-not-prevent-high-fat-diet-induced-metabolic-complications
#1
Bahareh Hekmatnejad, Vionnie W C Yu, William Addison, Vice Mandic, Martin Pellicelli, Alice Arabian, René St-Arnaud
FIAT (Factor Inhibiting ATF4-mediated Transcription) interacts with ATF4 to repress its transcriptional activity. We performed a phenotypic analysis of Fiat-deficient male mice (Fiat(-/Y)) at 8 and 16 weeks of age. Fiat(-/Y) mice appeared normal at birth and weight gain was comparable between genotypes. μCT analysis of proximal femur demonstrated 46% and 13% age-dependent increases in trabecular bone volume and thickness, respectively, in Fiat(-/Y) mice. Cortical bone measurements at the femoral midshaft revealed a significant increase in cortical thickness in older Fiat(-/Y) mice...
December 1, 2016: Endocrinology
https://www.readbyqxmd.com/read/27894216/bone-effects-of-canagliflozin-a-sodium-glucose-co-transporter-2-inhibitor-in-patients-with-type-2-diabetes-mellitus
#2
Thomas C Blevins, Azeez Farooki
Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor approved for the treatment of type 2 diabetes mellitus (T2DM), lowers blood glucose by inhibiting renal glucose reabsorption and increasing urinary glucose excretion. It has been reported that SGLT2 inhibitors may have potential adverse effects on bone, including increased fracture risk and decreased bone mineral density (BMD). Across clinical studies, canagliflozin was not associated with meaningful changes in serum or urine calcium, vitamin D, or parathyroid hormone...
November 28, 2016: Postgraduate Medicine
https://www.readbyqxmd.com/read/27889689/osteoarthritis-and-type-2-diabetes-mellitus-what-are-the-links
#3
REVIEW
Alice Courties, Jérémie Sellam
Osteoarthritis (OA) is the most frequent joint disorder and one of the leading cause of disability. During a long time, it was considered as the consequence of aging and mechanical stress on cartilage. Recent advances in the knowledge of OA have highlighted that it is a whole joint disease with early modifications of synovium and subchondral bone but also that it is associated with obesity and metabolic syndrome through systemic mechanisms. In the past year, type 2 diabetes has been described in two meta-analyzes as an independent risk factor for OA...
November 5, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/27860330/phenotype-based-selection-of-bone-marrow-mesenchymal-stem-cell-derived-smooth-muscle-cells-for-elastic-matrix-regenerative-repair-in-abdominal-aortic-aneurysms
#4
Ganesh Swaminathan, Ivan Stoilov, Tom Broekelmann, Robert Mecham, Anand Ramamurthi
Chronic proteolytic disruption of elastic fibers within the abdominal aortic wall results in wall vessel expansion to form rupture-prone abdominal aortic aneurysms (AAA). Arresting AAA growth is not possible since adult vascular smooth muscle cells (SMCs) poorly auto-regenerate and repair elastic fibers. Thus, there is a need to identify alternate cell sources capable of robust elastic matrix assembly to overcome elastolysis in the AAA wall. Previously, we demonstrated the superior elastogenic properties of rat bone marrow mesenchymal stem cell (BM-MSC)-derived SMCs (BM-SMCs) relative to aneurysmal and healthy rat aortic SMCs...
November 11, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27845859/cross-talk-between-muscle-and-bone-in-postmenopausal-women-with-hypovitaminosis-d
#5
M Vuksanovic, G Mihajlovic, T Beljic Zivkovic, A Gavrilovic, B Arsenovic, J Zvekic Svorcan, M Marjanovic Petkovic, S Vujovic
OBJECTIVES: Visceral fat is more harmful than subcutaneous fat. Women with high amounts of visceral fat have an increased risk of metabolic syndrome (MetS), insulin resistance and low level of serum vitamin D. METHODS: This was a prospective, randomized and controlled study. Postmenopausal women (n = 101) aged 45-70 years were included. The assessed parameters were: body mass index (BMI), waist circumference (WC), 25-hydroxyvitamin D (25-OHD) status, serum insulin and HOMA-IR, bone mineral density, total fat mass, fat mass index (FMI) measured by DXA, and muscle strength...
November 15, 2016: Climacteric: the Journal of the International Menopause Society
https://www.readbyqxmd.com/read/27835579/a-novel-benzofuran-derivative-acdb-induces-apoptosis-of-human-chondrosarcoma-cells-through-mitochondrial-dysfunction-and-endoplasmic-reticulum-stress
#6
Chen-Ming Su, Chien-Yu Chen, Tingting Lu, Yi Sun, Weimin Li, Yuan-Li Huang, Chun-Hao Tsai, Chih-Shiang Chang, Chih-Hsin Tang
Chondrosarcoma is one of the bone tumor with high mortality in respond to poor radiation and chemotherapy treatment. Here, we analyze the antitumor activity of a novel benzofuran derivative, 2-amino-3-(2-chlorophenyl)-6-(4-dimethylaminophenyl)benzofuran-4-yl acetate (ACDB), in human chondrosarcoma cells. ACDB increased the cell apoptosis of human chondrosarcomas without harm in chondrocytes. ACDB also enhanced endoplasmic reticulum (ER) stress, which was characterized by varieties in the cytosolic calcium levels and induced the expression of glucose-regulated protein (GRP) and calpain...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27832314/diets-high-in-fat-or-fructose-differentially-modulate-bone-health-and-lipid-metabolism
#7
Aditi Jatkar, Irwin J Kurland, Stefan Judex
Diets high in fat or carbohydrates can lead to obesity and diabetes, two interrelated conditions that have been associated with osteoporosis. Here, we contrasted the effects of a high fat (HF) versus fructose-enriched carbohydrate (CH) versus regular chow (SC) diet on bone morphology, fat content and metabolic balance in BALB/cByJ mice over a 15-week period. For 13 weeks, there were no differences in body mass between groups with small differences in the last 2 weeks. Even without the potentially confounding factor of altered body mass and levels of load bearing, HF consumption was detrimental to bone in the distal femur with lower trabecular bone volume fraction and thinner cortices than controls...
November 10, 2016: Calcified Tissue International
https://www.readbyqxmd.com/read/27818742/methodological-considerations-when-studying-the-skeletal-response-to-glucose-intolerance-using-the-diet-induced-obesity-model
#8
Elizabeth Rendina-Ruedy, Brenda J Smith
The prevalence of obesity and type 2 diabetes mellitus (T2DM) continues to rise, and as a result, research aimed at understanding the molecular basis for the co-morbidities has become an area of much scientific interest. Among the more recently recognized chronic complications of T2DM is the increased risk of fracture, especially hip fracture, that has been reported independent of bone mineral density (BMD). A widely used animal model to study how the development and progression of impaired glucose tolerance affect the skeleton has been the diet-induce obesity (DIO) model...
2016: BoneKEy Reports
https://www.readbyqxmd.com/read/27813678/animal-proteins-as-important-contributors-to-a-healthy-human-diet
#9
Ibrahim Elmadfa, Alexa L Meyer
Adequate protein intake is critical for health and development. Generally, protein of animal origin is of higher quality for humans owing to its amino acid pattern and good digestibility. When administered in mixtures it can enhance the quality of plant proteins, but it is often scarce in low-income communities, especially in young children, the elderly, and pregnant and lactating women, who have increased requirements and in whom high-quality protein also stimulates bone growth and maintenance. Although high protein intake was associated with increased type 2 diabetes mellitus risk, milk and seafood are good sources of branched chain amino acids and taurine, which act beneficially on glucose metabolism and blood pressure...
October 28, 2016: Annual Review of Animal Biosciences
https://www.readbyqxmd.com/read/27792161/maternal-dietary-vitamin-d-does-not-program-systemic-inflammation-and-bone-health-in-adult-female-mice-fed-an-obesogenic-diet
#10
Christopher R Villa, Jianmin Chen, Bijun Wen, Sandra M Sacco, Amel Taibi, Wendy E Ward, Elena M Comelli
Obesity is associated with systemic inflammation and impaired bone health. Vitamin D regulates bone metabolism, and has anti-inflammatory properties and epigenetic effects. We showed that exposure to high dietary vitamin D during pregnancy and lactation beneficially programs serum concentration of lipopolysaccharide (LPS) and bone structure in male offspring fed an obesogenic diet. Here we assessed if this effect is also apparent in females. C57BL/6J dams were fed AIN93G diet with high (5000 IU/kg diet) or low (25 IU/kg diet) vitamin D during pregnancy and lactation...
October 26, 2016: Nutrients
https://www.readbyqxmd.com/read/27742831/gm-csf-induces-inflammatory-macrophages-by-regulating-glycolysis-and-lipid-metabolism
#11
Yi Rang Na, Gyo Jung Gu, Daun Jung, Young Won Kim, Juri Na, Jin Sun Woo, Joo Youn Cho, Hyewon Youn, Seung Hyeok Seok
GM-CSF induces proinflammatory macrophages, but the underlying mechanisms have not been studied thus far. In this study, we investigated the mechanisms of how GM-CSF induces inflammatory macrophages. First, we observed that GM-CSF increased the extent of LPS-induced acute glycolysis in murine bone marrow-derived macrophages. This directly correlates with an inflammatory phenotype because glycolysis inhibition by 2-deoxyglucose abolished GM-CSF-mediated increase of TNF-α, IL-1β, IL-6, and IL-12p70 synthesis upon LPS stimulation...
October 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27740628/hedgehog-signaling-in-bone-regulates-whole-body-energy-metabolism-through-a-bone-adipose-endocrine-relay-mediated-by-pthrp-and-adiponectin
#12
Xu Zhang, Qianni Cheng, Yixiang Wang, Po Sing Leung, Kinglun Kingston Mak
Bone plays a role in energy metabolism, but the interplay between bone and other organs in this process is not completely understood. Here, we show that upregulated Hh signaling in bones results in increased whole-body energy expenditure, white adipose tissue (WAT) browning, hypoglycemia and skeletal muscle atrophy. We found that Hh signaling induces PTHrP secretion from bones and causes WAT browning. Injection of PTHrP-neutralizing antibody attenuates WAT browning and improves the circulating blood glucose level while high-fat diet treatment only rescues hypoglycemia...
October 14, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27732331/high-sclerostin-and-dickkopf-1-dkk-1-serum-levels-in-children-and-adolescents-with-type-1-diabetes-mellitus
#13
Maria Felicia Faienza, Annamaria Ventura, Maurizio Delvecchio, Anna Fusillo, Laura Piacente, Gabriella Aceto, Graziana Colaianni, Silvia Colucci, Luciano Cavallo, Maria Grano, Giacomina Brunetti
CONTEXT: Childhood type 1 diabetes (T1DM) is associated with decreased bone mass. Sclerostin and dickkopf-1 (DKK-1) are Wnt inhibitors which regulate bone formation. OBJECTIVE: To evaluate sclerostin and DKK-1 levels in TD1M children and to analyze the influence of the glycaemic control on bone health. DESIGN AND SETTING: Cross-sectional study conducted at a clinical research center. Partecipants: One hundred and six T1DM subjects (12.2 ± 4 years), 66 on multiple daily injections (MDI) and 40 on continuous subcutaneous infusion of insulin (CSII), and 80 controls...
October 12, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27704164/human-multipotent-adult-progenitor-cells-enhance-islet-function-and-revascularisation-when-co-transplanted-as-a-composite-pellet-in-a-mouse-model-of-diabetes
#14
João Paulo M C M Cunha, Gunter Leuckx, Peter Sterkendries, Hannelie Korf, Gabriela Bomfim-Ferreira, Lutgart Overbergh, Bart Vaes, Harry Heimberg, Conny Gysemans, Chantal Mathieu
AIMS/HYPOTHESIS: Hypoxia in the initial days after islet transplantation leads to considerable loss of islet mass and contributes to disappointing outcomes in the clinical setting. The aim of the present study was to investigate whether co-transplantation of human non-endothelial bone marrow-derived multipotent adult progenitor cells (MAPCs), which are non-immunogenic and can secrete angiogenic growth factors during the initial days after implantation, could improve islet engraftment and survival...
January 2017: Diabetologia
https://www.readbyqxmd.com/read/27698344/maternal-vitamin-d-beneficially-programs-metabolic-gut-and-bone-health-of-mouse-male-offspring-in-an-obesogenic-environment
#15
C R Villa, J Chen, B Wen, S M Sacco, A Taibi, W E Ward, E M Comelli
BACKGROUND/OBJECTIVES: Vitamin D is an anti-inflammatory nutrient and a determinant of bone health. Some prospective studies suggest that maternal vitamin D status is positively associated with offspring bone mass. We found that serum concentrations of lipopolysaccharide (LPS), an inflammatory molecule related to adiposity, insulin resistance and bone resorption, is lower in healthy mouse offspring exposed to high dietary vitamin D during pregnancy and lactation. LPS reaches the circulation via the gut...
October 25, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27695036/differential-effects-of-dietary-fat-content-and-protein-source-on-bone-phenotype-and-fatty-acid-oxidation-in-female-c57bl-6-mice
#16
Emily A Sawin, Bridget M Stroup, Sangita G Murali, Lucas M O'Neill, James M Ntambi, Denise M Ney
BACKGROUND: Glycomacropeptide (GMP) is a 64-amino acid glycophosphopeptide released from κ-casein during cheesemaking that promotes satiety, reduces body fat, increases bone mass and infers prebiotic and anti-inflammatory effects. The impact of adiposity and gender on bone health is unclear. OBJECTIVE: To determine how feeding female mice diets providing 60% Fat Kcal (high-fat) or 13% Fat Kcal (control) with either GMP or casein as the protein source impacts: body composition, ex vivo fatty acid oxidation, bone (femoral) biomechanical performance, and the relationship between body composition and bone...
2016: PloS One
https://www.readbyqxmd.com/read/27693963/high-glucose-prevents-osteogenic-differentiation-of-mesenchymal-stem-cells-via-lncrna-ak028326-cxcl13-pathway
#17
Boran Cao, Ning Liu, Wenbo Wang
BACKGROUND: High glucose (HG) often induces unfavorable effects on proliferation and differentiation of mesenchymal stem cells (MSCs). This study aimed to explore potential molecular pathways underlying HG functional mechanism during osteogenic differentiation of MSCs, involving lncRNA AK028326 and CXCL13. METHODS: Murine bone marrow-derived MSCs were cultured in osteogenic-inducing medium supplemented with high glucose level at 25mM or 5.5mM as normal control. Expression levels of lncRNA AK028326 and CXCL13 were measured by using real-time PCR...
September 28, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27692982/mtorc1-inhibition-with-rapamycin-exacerbates-adipose-tissue-inflammation-in-obese-mice-and-dissociates-macrophage-phenotype-from-function
#18
Vivian A Paschoal, Mariane T Amano, Thiago Belchior, Juliana Magdalon, Patricia Chimin, Maynara L Andrade, Milene Ortiz-Silva, Érique Castro, Alex S Yamashita, José Cesar Rosa Neto, Niels O Câmara, William T Festuccia
Genetic- and diet-induced obesity and insulin resistance are associated with an increase in mechanistic target of rapamycin complex (mTORC) 1 activity in adipose tissue. We investigated herein the effects of pharmacological mTORC1 inhibition in the development of adipose tissue inflammation induced by high-fat diet (HFD) feeding, as well as in the polarization, metabolism and function of bone marrow-derived macrophages (BMDM). For this, C57BL/6J mice fed with a standard chow diet or a HFD (60% of calories from fat) and treated with either vehicle (0...
September 28, 2016: Immunobiology
https://www.readbyqxmd.com/read/27689415/glucose-transporter-4-facilitates-insulin-stimulated-glucose-uptake-in-osteoblasts
#19
Zhu Li, Julie L Frey, G William Wong, Marie-Claude Faugere, Michael J Wolfgang, Jason K Kim, Ryan C Riddle, Thomas L Clemens
Recent studies have identified the osteoblast as an insulin responsive cell that participates in global energy homeostasis. Here, we show that glucose transporter-4 (Glut4) is required for insulin-dependent uptake and oxidation of glucose in mature osteoblasts. In primary cultures of mouse osteoblasts, insulin increased uptake and oxidation of (14)C-glucose in a dose-dependent fashion but did not significantly affect uptake or oxidation of (14)C-oleate. In vitro, undifferentiated osteoblasts expressed 3 high-affinity Gluts: Glut1, Glut4, and Glut3...
November 2016: Endocrinology
https://www.readbyqxmd.com/read/27683064/pthrp-derived-peptides-restore-bone-mass-and-strength-in-diabetic-mice-additive-effect-of-mechanical-loading
#20
Marta Maycas, Kevin A McAndrews, Amy Y Sato, Gretel G Pellegrini, Drew M Brown, Matthew R Allen, Lilian I Plotkin, Arancha R Gortazar, Pedro Esbrit, Teresita Bellido
There is an unmet need to understand the mechanisms underlying skeletal deterioration in diabetes mellitus (DM) and to develop therapeutic approaches to treat bone fragility in diabetic patients. We demonstrate herein that mice with type 1 DM induced by streptozotocin exhibited low bone mass, inferior mechanical and material properties, increased bone resorption, decreased bone formation, increased apoptosis of osteocytes, and increased expression of the osteocyte-derived bone formation inhibitor Sost/sclerostin...
September 28, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
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