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Metabolic Syndrome and Bone: Pharmacologically Induced Diabetes has Deleterious Effect on Bone in Growing Obese Rats

Metabolic syndrome and osteoporosis share similar risk factors. Also, patients with diabetes have a higher risk of osteoporosis and fracture. Liver manifestations, such as non-alcoholic steatohepatitis (NASH), of metabolic syndrome are further aggravated in diabetics and often lead to liver failure....

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Autores principales: Bagi, Cedo M., Edwards, Kristin, Berryman, Edwin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956015/
https://www.ncbi.nlm.nih.gov/pubmed/29196931
http://dx.doi.org/10.1007/s00223-017-0367-z
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author Bagi, Cedo M.
Edwards, Kristin
Berryman, Edwin
author_facet Bagi, Cedo M.
Edwards, Kristin
Berryman, Edwin
author_sort Bagi, Cedo M.
collection PubMed
description Metabolic syndrome and osteoporosis share similar risk factors. Also, patients with diabetes have a higher risk of osteoporosis and fracture. Liver manifestations, such as non-alcoholic steatohepatitis (NASH), of metabolic syndrome are further aggravated in diabetics and often lead to liver failure. Our objective was to create a rat model of human metabolic syndrome and determine the long-term impact of early-onset T1D on bone structure and strength in obese growing rats. Male rats were given either standard chow and RO water (Controls) or a high-fat, high-cholesterol diet and sugar water containing 55% fructose and 45% glucose (HFD). A third group of rats received the HFD diet and a single dose of streptozotocin to induce type 1 diabetes (HFD/Sz). Body weight and glucose tolerance tests were conducted several times during the course of the study. Serum chemistry, liver enzymes, and biomarkers of bone metabolism were evaluated at 10 and 28 weeks. Shear wave elastography and histology were used to assess liver fibrosis. Cancellous bone structure and cortical bone geometry were evaluated by mCT and strength by the 3-point bending method. Body mass and fat accumulation was significantly higher in HFD and HFD/Sz rats compared to Controls. Rats in both the HFD and HFD/Sz groups developed NASH, although the change was more severe in diabetic rats. Although both groups of obese rats had larger bones, their cancellous structure and cortical thickness were reduced, resulting in diminished strength that was further aggravated by diabetes. The HFD and HFD/Sz rats recapitulate MeSy in humans with liver pathology consistent with NASH. Our data provide strong indication that obesity accompanied by type 1 diabetes significantly aggravates comorbidities of MeSy, including the development of osteopenia and weaker bones. The juvenile rat skeleton seems to be more vulnerable to damage imposed by obesity and diabetes and may offer a model to inform the underlying pathology associated with the unusually high fracture rates in obese adults with diabetes.
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spelling pubmed-59560152018-05-18 Metabolic Syndrome and Bone: Pharmacologically Induced Diabetes has Deleterious Effect on Bone in Growing Obese Rats Bagi, Cedo M. Edwards, Kristin Berryman, Edwin Calcif Tissue Int Original Research Metabolic syndrome and osteoporosis share similar risk factors. Also, patients with diabetes have a higher risk of osteoporosis and fracture. Liver manifestations, such as non-alcoholic steatohepatitis (NASH), of metabolic syndrome are further aggravated in diabetics and often lead to liver failure. Our objective was to create a rat model of human metabolic syndrome and determine the long-term impact of early-onset T1D on bone structure and strength in obese growing rats. Male rats were given either standard chow and RO water (Controls) or a high-fat, high-cholesterol diet and sugar water containing 55% fructose and 45% glucose (HFD). A third group of rats received the HFD diet and a single dose of streptozotocin to induce type 1 diabetes (HFD/Sz). Body weight and glucose tolerance tests were conducted several times during the course of the study. Serum chemistry, liver enzymes, and biomarkers of bone metabolism were evaluated at 10 and 28 weeks. Shear wave elastography and histology were used to assess liver fibrosis. Cancellous bone structure and cortical bone geometry were evaluated by mCT and strength by the 3-point bending method. Body mass and fat accumulation was significantly higher in HFD and HFD/Sz rats compared to Controls. Rats in both the HFD and HFD/Sz groups developed NASH, although the change was more severe in diabetic rats. Although both groups of obese rats had larger bones, their cancellous structure and cortical thickness were reduced, resulting in diminished strength that was further aggravated by diabetes. The HFD and HFD/Sz rats recapitulate MeSy in humans with liver pathology consistent with NASH. Our data provide strong indication that obesity accompanied by type 1 diabetes significantly aggravates comorbidities of MeSy, including the development of osteopenia and weaker bones. The juvenile rat skeleton seems to be more vulnerable to damage imposed by obesity and diabetes and may offer a model to inform the underlying pathology associated with the unusually high fracture rates in obese adults with diabetes. Springer US 2017-12-01 2018 /pmc/articles/PMC5956015/ /pubmed/29196931 http://dx.doi.org/10.1007/s00223-017-0367-z Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Research
Bagi, Cedo M.
Edwards, Kristin
Berryman, Edwin
Metabolic Syndrome and Bone: Pharmacologically Induced Diabetes has Deleterious Effect on Bone in Growing Obese Rats
title Metabolic Syndrome and Bone: Pharmacologically Induced Diabetes has Deleterious Effect on Bone in Growing Obese Rats
title_full Metabolic Syndrome and Bone: Pharmacologically Induced Diabetes has Deleterious Effect on Bone in Growing Obese Rats
title_fullStr Metabolic Syndrome and Bone: Pharmacologically Induced Diabetes has Deleterious Effect on Bone in Growing Obese Rats
title_full_unstemmed Metabolic Syndrome and Bone: Pharmacologically Induced Diabetes has Deleterious Effect on Bone in Growing Obese Rats
title_short Metabolic Syndrome and Bone: Pharmacologically Induced Diabetes has Deleterious Effect on Bone in Growing Obese Rats
title_sort metabolic syndrome and bone: pharmacologically induced diabetes has deleterious effect on bone in growing obese rats
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956015/
https://www.ncbi.nlm.nih.gov/pubmed/29196931
http://dx.doi.org/10.1007/s00223-017-0367-z
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