Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
Centre for Metabolism, Obesity and Diabetes Research, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
J Physiol. 2022 Nov;600(21):4677-4693. doi: 10.1113/JP283469. Epub 2022 Sep 25.
Ketogenic diets (KDs) are a popular tool used for weight management. Studies in mice have demonstrated that KDs reduce food intake, increase energy expenditure and cause weight loss. These studies were completed at room temperature, a condition below the animal's thermal neutral zone which induces thermal stress. As energy intake and expenditure are sensitive to environmental temperature it is not clear if a KD would exert the same beneficial effects under thermal neutral conditions. Adherence to restrictive diets is poor and consequently it is important to examine the effects, and underlying mechanisms, of cycling from a ketogenic to an obesogenic diet. The purpose of the current study was to determine if housing temperature impacted the effects of a KD in obese mice and to determine if the mechanisms driving KD-induced weight loss reverse when mice are switched to an obesogenic high fat diet. We demonstrate that KD-induced reductions in food intake, increases in energy expenditure, weight loss and improvements in glucose homeostasis are not dependent upon housing temperature. KD-induced weight loss seems to be largely explained by reductions in caloric intake while cycling mice back to an obesogenic diet following a period of KD feeding leads to hyperphagia-induced weight gain. Collectively, our results suggest that prior findings with mice fed a KD at room temperature are likely not an artifact of how mice were housed and that initial changes in weight when transitioning from an obesogenic to a ketogenic diet or back are largely dependent on food intake. KEY POINTS: Ketogenic diets reduce food intake, increase energy expenditure and cause weight loss in rodents Prior preclinical studies have been completed at room temperature, a condition which induces thermal stress and limits clinical translatability Here it is demonstrated that ketogenic diet-induced reductions in food intake, increases in energy expenditure, weight loss and improvements in glucose homeostasis are similar in mice housed at room temperature or thermal neutrality Ketogenic diet-induced reductions in food intake appear to explain a large degree of weight loss. Similarly, switching mice from a ketogenic to an obesogenic diet leads to hyperphagia-mediated weight gain.
生酮饮食（KDs）是一种用于体重管理的常用工具。在小鼠中的研究表明，KDs 可减少食物摄入、增加能量消耗并导致体重减轻。这些研究是在室温下完成的，室温低于动物的热中性区，会导致热应激。由于能量摄入和消耗对环境温度敏感，因此尚不清楚在热中性条件下，KD 是否会产生相同的有益效果。限制饮食的依从性很差，因此检查从生酮饮食到肥胖饮食的循环对能量摄入和消耗的影响以及潜在机制非常重要。本研究的目的是确定环境温度是否会影响肥胖小鼠中 KD 的效果，以及当小鼠切换到肥胖高脂肪饮食时，驱动 KD 诱导的体重减轻的机制是否会逆转。我们证明，KD 诱导的食物摄入量减少、能量消耗增加、体重减轻和葡萄糖稳态改善不依赖于环境温度。KD 诱导的体重减轻似乎在很大程度上归因于热量摄入的减少，而在 KD 喂养一段时间后，当小鼠重新回到肥胖饮食时，摄食过度引起的体重增加。总的来说，我们的结果表明，先前在室温下用 KD 喂养的小鼠的研究结果可能不是由于小鼠的饲养方式造成的，并且从肥胖饮食向生酮饮食或反之过渡时体重的最初变化在很大程度上取决于食物摄入。要点：生酮饮食可减少啮齿动物的食物摄入、增加能量消耗并导致体重减轻。先前的临床前研究是在室温下完成的，这种条件会引起热应激并限制临床转化。本研究表明，在室温或热中性条件下饲养的小鼠中，KD 诱导的食物摄入量减少、能量消耗增加、体重减轻和葡萄糖稳态改善相似。KD 诱导的食物摄入量减少似乎解释了体重减轻的很大一部分。同样，将小鼠从生酮饮食切换到肥胖饮食会导致摄食过度引起的体重增加。
