A Cocoa Butter-Based Ketogenic Diet Fails to Improve Glucose Homeostasis and Promote Weight Loss in Obese Mice

Background: High-fat and very low-carbohydrate based ketogenic diets have gained considerable popularity as a non-pharmacological strategy for treating obesity due to their potential to enhance weight loss and improve glucose homeostasis. However, the effectiveness of a ketogenic diet towards metabolic health is equivocal. Methods: Male and female mice were fed a 60% cocoa butter fat-based high-fat diet for 16-weeks to induce obesity, following which mice were transitioned to either an 85% cocoa butter fat-based ketogenic diet (KD) , a 10% cocoa butter fat-based low-fat diet (LFD) , or maintained on a high-fat diet for an additional 8-weeks. All experimental diets were matched for sucrose and protein content, and contained an identical micronutrient profile, with complex carbohydrates being the primary carbohydrate source in the LFD. Results: The transition to a KD was ineffective at inducing significant body fat loss, improving glucose homeostasis, or enhancing insulin sensitivity in obese male and female mice. Alternatively, obese male and female mice transitioned to a LFD exhibited a marked decrease in body weight, which was primarily attributed to a loss of adiposity, and an improved glucose tolerance during an intraperitoneal glucose tolerance test. Despite the improvements in glucose tolerance, insulin sensitivity remained impaired in obese male mice transitioned to a LFD, whereas it was improved in obese female mice. These salutary actions attributed to a transition to a LFD resulting in beneficial body composition changes and improved glucose tolerance, may in part be due to the trend to mild reductions and increases in food intake and energy expenditure, respectively. Conclusions: Our findings suggest that careful consideration should be taken when consuming a KD as a non-pharmacological strategy for treating obesity, whereas consumption of a diet low in saturated fat and rich in complex carbohydrates imparts numerous beneficial actions. Disclosure A.A.Greenwell: None. G.Lopaschuk: None. R.A.Batran: None. J.R.Ussher: None. C.T.Saed: None. S.Tabatabaei dakhili: None. K.Ho: None. K.Gopal: None. J.S.F.Chan: None. O.Kaczmar: None. S.A.Dyer: None. F.Eaton: None.