ABSTRACT
OBJECTIVES: The aim of this experimental study was to evaluate the expression of 4 genes (osteocalcin, sclerostin (SOST), insulin receptor, and transcription factor forkhead box protein (FOXO1) in the bone cells of Goto-Kakizaki (GK) rats and the expression of these genes in response to bariatric surgery. METHODS: We designed an experimental study with 3 arms (Wistar rats, nonoperated GK rats, and GK rats with gastrojejunal bypass). Gene expression (osteocalcin, insulin receptor, FOXO1, SOST) was measured at baseline and after surgery. Plasma levels of glucose, insulin, homeostasis model assessment (HOMA), glucagon-like peptide 1 (GLP-1), and the production of insulin were measured at baseline and at 60 minutes by pancreatic islets. RESULTS: GK rats had decreased levels of expression of osteocalcin (50.86 ± 19.21 versus 16.78 ± 22.11, P = .031), insulin receptor (1.45 ± .44 versus .54 ± .35, P = .020), and SOST (.92 ± .05 versus .43 ± .47, P = .048) compared with Wistar rats. Gene expression in GK rats, operated and nonoperated, was similar. In nonoperated GK rats, there was a negative correlation between the SOST gene and plasma insulin (r:-.786, P = .021) and the production of insulin by pancreatic islets at 60 minutes (r:-0.857, P = .014). GLP-1 increased after surgery. CONCLUSION: Diabetic GK rats presented a reduced expression of the osteocalcin, insulin receptor, and SOST genes. There was an inverse relationship between SOST and plasma and local insulin. We found no changes in the expression of bone genes that regulate energy metabolism after gastrojejunal bypass.
Subject(s)
Bone Morphogenetic Proteins/biosynthesis , Bone and Bones/metabolism , Energy Metabolism/physiology , Forkhead Transcription Factors/biosynthesis , Gene Expression Regulation , Nerve Tissue Proteins/biosynthesis , Osteocalcin/biosynthesis , Receptor, Insulin/biosynthesis , Animals , Bariatric Surgery , Bone Morphogenetic Proteins/genetics , Bone and Bones/pathology , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Forkhead Transcription Factors/genetics , Genetic Markers/genetics , Genotype , Male , Nerve Tissue Proteins/genetics , Obesity/genetics , Obesity/metabolism , Obesity/pathology , Osteocalcin/genetics , Rats , Rats, Wistar , Receptor, Insulin/geneticsABSTRACT
BACKGROUND: The aim of this study was to evaluate gene expression of bone remodeling markers in type 2 diabetic Goto-Kakizaki (GK) nonobese rats after gastrojejunal bypass and sleeve gastroplasty and their relationship with hormonal parameters. METHODS: We designed an experimental study in three groups of GK rats (nonoperated gastrojejunal bypass and sleeve gastroplasty). Gene expression of markers of bone remodeling and levels of insulin, leptin, and glucagon-like peptide-1 (GLP-1) were determined. RESULTS: GK rats had decreased levels of osteocalcin expression compared with Wistar rats. Gene expression of markers of bone remodeling in GK rats was similar in the three groups studied, although there was a trend to decreased receptor activator for nuclear factor κ B ligand (RANKL) in gastroplasty rats. Significant differences in the osteocalcin/RANKL ratio were observed between controls and gastrojejunal bypass rats compared with gastroplasty rats. The behavior of gastrointestinal hormones was antagonistic (GLP-1 gastrojejunal bypass 1.54 ± 0.24 ng/ml vs. GLP-1 gastroplasty 0.673 ± 0.09, p = 0.0001; leptin gastrojejunal bypass 1,178 ± 0.474 pg/ml vs. leptin gastroplasty 7,391 ± 4,054 pg/ml, p = 0.002). There was a reduction in leptin in the bypass group associated with an increase in gastrectomized rats. In gastrectomized rats, there was a trend toward an inverse relationship between leptin and RANKL (r = -0.771, p = 0.072). This relationship was more marked in the totality of operated rats, n = 12 (r = -0.608, p = 0.036). CONCLUSION: Our results show a more favorable profile of sleeve gastroplasty on bone remodeling. There was a trend to an increase in the expression of the osteocalcin gene, which is probably mediated by increased expression of leptin that inhibits the expression of RANKL.
Subject(s)
Bone Remodeling/genetics , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/surgery , Gastric Bypass , Gastroplasty , Osteocalcin/genetics , RANK Ligand/genetics , Animals , Biomarkers/analysis , Disease Models, Animal , Gene Expression , Male , Osteocalcin/biosynthesis , RANK Ligand/biosynthesis , Rats , Rats, WistarABSTRACT
BACKGROUND: The effects of type 2 diabetes on bone mass and microstructure are not clear. The aim of this study was to evaluate bone microstructural properties and volumetric bone mineral density (vBMD) in type 2 diabetic Goto-Kakizaki non-obese rats after gastrojejunal bypass and their relationship with hormonal parameters. METHODS: We designed an experimental study in Goto-Kakizaki rats with and without gastrojejunal bypass, performing densitometric and microstructural studies of the distal femur using X-ray computed microtomography (micro-CT). Levels of insulin, glucagon, leptin, and glucagon-like peptide-1 (GLP-1) were also determined. RESULTS: We observed reduced cortical (1,488.92 ± 98.2 vs. 1,727.92 ± 133.45 mg/cm(3), p = 0.028) and trabecular (180.8 ± 9 vs. 261.23 ± 45.54 mg/cm(3), p = 0.036) vBMD in operated rats. Bone volume fraction (BV/TV) and trabecular connectivity were reduced in operated rats, while there was a reduction in cortical thickness and an increase in rod-like trabeculae at the expense of plate-like trabeculae. Leptin was reduced (1,042 ± 549 vs. 2,447 ± 1,035 pg/ml, p = 0.05) and GLP-1 increased (1.62 ± 0.32 vs. 0.96 ± 0.1 ng/ml, p = 0.008) but only leptin showed a significant association with vBMD CONCLUSIONS: In type 2 diabetic Goto-Kakizaki rats, gastrojejunal bypass produces a reduction in cortical and trabecular bone mineral density and a deterioration in bone quality that could be explained, in part, by the reduction in leptin levels.
