Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
Am J Physiol Endocrinol Metab. 2022 Jul 1;323(1):E8-E20. doi: 10.1152/ajpendo.00435.2021. Epub 2022 May 16.
High-fat and very low-carbohydrate based ketogenic diets have gained considerable popularity as a nonpharmacological strategy for obesity, due to their potential to enhance weight loss and improve glucose homeostasis. However, the effectiveness of a ketogenic diet toward metabolic health is equivocal. To better understand the impact of ketogenic diets in obesity, male and female mice were fed a 60% cocoa butter-based high-fat diet for 16-wk to induce obesity, following which mice were transitioned to either an 85% cocoa butter fat-based ketogenic diet, a 10% cocoa butter fat-based low-fat diet, or maintained on a high-fat diet for an additional 8-wk. 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 low-fat diet. The transition to a ketogenic diet was ineffective at promoting significant body fat loss and improving glucose homeostasis in obese male and female mice. Alternatively, obese male and female mice transitioned to a low-fat and high-complex carbohydrate diet exhibited beneficial body composition changes and improved glucose tolerance that may, in part, be attributed to a mild decrease in food intake and a mild increase in energy expenditure. Our findings support the consumption of a diet low in saturated fat and rich in complex carbohydrates as a potential dietary intervention for the treatment of obesity and obesity-induced impairments in glycemia. Furthermore, our results suggest that careful consideration should be taken when considering a ketogenic diet as a nonpharmacological strategy for obesity. It has been demonstrated that ketogenic diets may be a nutritional strategy for alleviating hyperglycemia and promoting weight loss in obesity. However, there are a number of inconsistencies with many of these studies, especially with regard to the macronutrient and micronutrient compositions of the diets being compared. Our work demonstrates that a ketogenic diet that is both micronutrient-matched and isoproteic with its comparator diets fails to improve glycemia or promote weight loss in obese mice.
高脂肪和极低碳水化合物的生酮饮食作为一种非药物策略，因其具有增强体重减轻和改善葡萄糖稳态的潜力，在肥胖症领域已经获得了相当大的关注。然而，生酮饮食对代谢健康的有效性仍存在争议。为了更好地理解生酮饮食在肥胖症中的影响，雄性和雌性小鼠被喂食 60%可可脂的高脂肪饮食 16 周以诱导肥胖，之后将小鼠转换为 85%可可脂的生酮饮食、10%可可脂的低脂饮食或继续喂食高脂肪饮食 8 周。所有实验饮食均匹配蔗糖和蛋白质含量，并含有相同的微量营养素谱，复杂碳水化合物是低脂饮食中的主要碳水化合物来源。向生酮饮食的转换并不能有效促进肥胖雄性和雌性小鼠显著的体脂减少和改善葡萄糖稳态。相反，转换为低脂和高复合碳水化合物饮食的肥胖雄性和雌性小鼠表现出有益的身体成分变化和改善的葡萄糖耐量，这可能部分归因于食物摄入量的轻度减少和能量消耗的轻度增加。我们的研究结果支持摄入低饱和脂肪和富含复杂碳水化合物的饮食作为治疗肥胖症和肥胖引起的血糖损害的潜在饮食干预措施。此外，我们的研究结果表明，在考虑生酮饮食作为肥胖症的非药物策略时，应谨慎考虑。已经证明，生酮饮食可能是缓解肥胖症高血糖和促进体重减轻的营养策略。然而，这些研究中有许多存在不一致之处，尤其是在比较的饮食的宏量营养素和微量营养素组成方面。我们的工作表明，与对照饮食相比，既在微量营养素上匹配又在蛋白质上保持等蛋白的生酮饮食不能改善肥胖小鼠的血糖或促进体重减轻。
