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

Abstract

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.

Rehmannia glutinosa Libosch Extracts Prevent Bone Loss and Architectural Deterioration and Enhance Osteoblastic Bone Formation by Regulating the IGF-1/PI3K/mTOR Pathway in Streptozotocin-Induced Diabetic Rats

“…There is growing evidence supporting that DM may result in disturbance of bone metabolism [6]. Several studies [7,8] demonstrated that DM induced bone loss and reduced bone mechanical properties with a decreased osteoblastic bone formation rate.…”

Acid-base disorders and the impact on metabolic bone disease in hemodialysis patients

“…D levels were calculated in lab rats with renal failure that were administered hydrochloric acid in order to produce metabolic acidosis and non-acidotic uremic controls; there was no significant difference in 1,25-Vit. D levels throughout these groups 32,33 .…”

Higher serum apolipoprotein B level will reduce the bone mineral density and increase the risk of osteopenia or osteoporosis in adults

“…The protein fraction of lipoproteins is called apolipoprotein (Apo) (Mooser et al, 1997), and has important physiological functions in lipoprotein metabolism (Florea et al, 2022). Apolipoprotein B is synthesized in the liver (Bell et al, 2011) and is the main structural protein of LDL (Yaseen et al, 2021), accounting for most of the total protein content of LDL, with its measurement directly reflecting LDL levels (Sun et al, 2020). Elevated obesity (weight overload) leads to elevated levels of apolipoprotein B in the blood (Manapurath et al, 2022), which decrease with exercise, vegetarianism, and hypolipidemia (Hostmark et al, 1993;Gao et al, 2018;Stanton et al, 2022).…”