Effects of Low Fat Versus High Fat Cheese on Glucose Homeostasis and Hepatic Lipid Metabolism in Prediabetic and Type 2 Diabetic Rats

• Author / Creator

  Hanning, Anik R. Z.

• Background: Type 2 diabetes (T2D) is a disease characterized by insulin resistance and pancreatic beta cell failure. Lifestyle interventions, including dietary interventions, are the first line of treatment for this disease. At present, Canada’s Food Guide recommends choosing low fat cheese over high fat cheese, however, current literature suggests a more complex relationship exists between cheese consumption and risk of T2D. Several fatty acids abundant in cheese have been shown independently to have beneficial effects on glucose homeostasis. Therefore, it is of particular interest whether low fat cheese and high fat cheese affect diabetes outcomes differently. Objectives: (1) To determine the impacts of cheese feeding on in vivo responses to glucose and insulin in prediabetic and T2D rats. (2) To explore the mechanisms by which cheese affects metabolism in prediabetic rats using an untargeted metabolomic analysis. (3) To use the results of the in vivo studies and metabolomics assays to direct additional investigations of the effects of cheese feeding in prediabetic rats. Methods: Two cohorts of rats, one prediabetic model (8-week old Sprague Dawley rats), and one T2D model (retired male Sprague Dawley breeder rats, 5-6 months old), were used. For each cohort, N = 64 animals were randomized to receive high fat diet (HFD) or low fat diet (LFD) for four weeks. In the T2D model, HFD rats underwent streptozotocin (STZ) administration at week 5 to induce a T2D phenotype. At the start of week 6, all HFD-fed animals (prediabetic and T2D models) were randomized to either continue on HFD or begin one of two cheese diets: HFD + high fat cheese (HFD+HFCh), or HFD + low fat cheese (HFD+LFCh) diet. HFD and cheese diets were isocaloric and matched for macronutrient composition. After 7-8 weeks of feeding, rats underwent either an oral glucose tolerance test (OGTT) or insulin tolerance test (ITT), and were euthanized the following week for tissue collection. In the prediabetic cohort, serum was sent for metabolomic analysis, and both the serum and liver lipidome were analyzed. Further, histology was conducted in a sub-sample of prediabetic rats’ livers. Results: Food intake and body weight were similar between groups in both cohorts. There was no effect of diet on HOMA-IR, glucose-insulin AUC index, or fasted insulin and glucose in either cohort. In the T2D cohort OGTT blood glucose was significantly higher in the HFD+HFCh group and HFD groups, relative to LFD, while HFD+LFCh was not. In the prediabetic cohort, both HFD+LFCh and HFD+HFCh groups demonstrated improved insulin sensitivity relative to HFD during an ITT, while OGTT blood glucose was unaffected by diet. Metabolomic analyses revealed alterations in several phosphatidylcholine metabolites in serum of cheese-fed, prediabetic rats, while overall serum lipids remained unaffected by diet. Hepatic triglyceride accumulation was increased in prediabetic HFD+LFCh, with cholesterol ester accumulation also increased, but not reaching significance. A similar trend was observed in HFD+HFCh. Liver histology revealed markedly increased oil red-O staining in the livers of prediabetic animals fed cheese. Conclusion: T2D rats that consumed HFD+LFCh had improved glucose tolerance that was not explained by body weight or insulin tolerance changes. Prediabetic rats that consumed either HFD+LFCh or HFD+HFCh demonstrated improved insulin sensitivity during an ITT. These rats also demonstrated increased liver triglyceride and cholesterol ester accumulation. This may have been due to altered phosphatidylcholine metabolism. These data suggest that either HFCh or LFCh may improve insulin sensitivity in a prediabetic model, while only LFCh improves glucose tolerance in a model of T2D.

• Subjects / Keywords

  • Cheese
  • Dairy Fat
  • Type 2 Diabetes
  • Prediabetes

• Graduation date

  Fall 2017

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R38W38G7D

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.