Obesity and Type 2 Diabetes, Not a Diet High in Fat, Sucrose, and Cholesterol, Negatively Impacts Bone Outcomes in the Hyperphagic Otsuka Long Evans Tokushima Fatty Rat

Bone. 2017 Dec;105:200-211. doi: 10.1016/j.bone.2017.09.003. Epub 2017 Sep 9.


Background: Obesity and type 2 diabetes (T2D) increase fracture risk; however, the association between obesity/T2D may be confounded by consumption of a diet high in fat, sucrose, and cholesterol (HFSC).

Objective: The study objective was to determine the main and interactive effects of obesity/T2D and a HFSC diet on bone outcomes using hyperphagic Otuska Long Evans Tokushima Fatty (OLETF) rats and normophagic Long Evans Tokushima Otsuka (LETO) controls.

Methods: At 8weeks of age, male OLETF and LETO rats were randomized to either a control (CON, 10 en% from fat as soybean oil) or HFSC (45 en% from fat as soybean oil/lard, 17 en% sucrose, and 1wt%) diet, resulting in four treatment groups. At 32weeks, total body bone mineral content (BMC) and density (BMD) and body composition were measured by dual-energy X-ray absorptiometry, followed by euthanasia and collection of blood and tibiae. Bone turnover markers and sclerostin were measured using ELISA. Trabecular microarchitecture of the proximal tibia and geometry of the tibia mid-diaphysis were measured using microcomputed tomography; whole-bone and tissue-level biomechanical properties were evaluated using torsional loading of the tibia. Two-factor ANOVA was used to determine main and interactive effects of diet (CON vs. HFSC) and obesity/T2D (OLETF vs. LETO) on bone outcomes.

Results: Hyperphagic OLEFT rats had greater final body mass, body fat, and fasting glucose than normophagic LETO, with no effect of diet. Total body BMC and serum markers of bone formation were decreased, and bone resorption and sclerostin were increased in obese/T2D OLETF rats. Trabecular bone volume and microarchitecture were adversely affected by obesity/T2D, but not diet. Whole-bone and tissue-level biomechanical properties of the tibia were not affected by obesity/T2D; the HFSC diet improved biomechanical properties only in LETO rats.

Conclusions: Obesity/T2D, regardless of diet, negatively impacted the balance between bone formation and resorption and trabecular bone volume and microarchitecture in OLETF rats.

Keywords: Bone; Bone turnover markers; Obesity; Trabecular microarchitecture; Type 2 diabetes; Western diet.

MeSH terms

  • Animals
  • Biomarkers / blood
  • Biomechanical Phenomena
  • Body Weight
  • Bone Remodeling
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / pathology*
  • Bone and Bones / physiopathology
  • Cancellous Bone / pathology
  • Cholesterol / adverse effects*
  • Collagen / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / pathology
  • Diaphyses / pathology
  • Diaphyses / physiopathology
  • Diet, High-Fat*
  • Glycation End Products, Advanced / metabolism
  • Hyperphagia / blood
  • Hyperphagia / complications*
  • Hyperphagia / pathology
  • Minerals / metabolism
  • Obesity / blood
  • Obesity / complications*
  • Obesity / pathology
  • Rats, Inbred OLETF
  • Sucrose / adverse effects*
  • Tibia / pathology
  • Tibia / physiopathology
  • X-Ray Microtomography


  • Biomarkers
  • Glycation End Products, Advanced
  • Minerals
  • Sucrose
  • bone ash
  • Collagen
  • Cholesterol