目的：研究不同运动联合饮食干预对营养性肥胖小鼠的减肥效果和骨骼肌脂代谢的影响，旨在探究一种健康有效的运动与饮食结合的减肥方法。方法：对200只健康雄性小鼠进行8周高脂饮食干预，建立肥胖模型。将肥胖鼠（56只）随机分为：高脂饮食组（HFD）、生酮饮食组（KD）、低脂饮食组（LFD）、生酮饮食结合高强度间歇运动组（KH）、生酮饮食结合中等强度持续运动组（KM）、低脂饮食结合高强度间歇运动组（LH）、低脂饮食结合中等强度持续运动组（LM）。干预5周，运动6天/周。干预结束后测血清总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、游离脂肪酸、脂联素、瘦素。皮下脂肪组织重量，内脏脂肪组织重量及切片。骨骼肌pAMPK/AMPK、PGC-1α、PPARα、CPT-1蛋白表达和Acadl、Acox1、Ehhadh、Mcad的mRNA表达水平。结果：生酮饮食比低脂饮食能有效降低小鼠摄食量和体脂率，增强小鼠骨骼肌AMPK磷酸化水平和脂肪酸β氧化酶Ehhadh基因表达水平。生酮饮食结合运动比低脂饮食结合运动能有效降低小鼠Lee’s指数和体脂率。高强度间歇运动结合饮食干预比中等强度持续运动结合饮食干预能有效降低小鼠Lee’s指数和体脂率。生酮饮食结合运动比低脂饮食结合运动能有效升高血液高密度脂蛋白胆固醇含量，降低甘油三酯含量，但也可导致低密度脂蛋白胆固醇含量升高。在生酮饮食或低脂饮食干预下，饮食结合运动干预比单纯饮食干预能有效提高小鼠骨骼肌脂肪酸氧化供能通路相关蛋白基因的表达。生酮饮食干预或低脂饮食干预下，高强度间歇运动比中等强度持续运动能有效提高小鼠骨骼肌脂肪酸氧化供能通路蛋白基因的表达。结论： 1．五周KD干预和LFD干预均能改善肥胖，KD比LFD更有效降低肥胖小鼠体脂率，升高肥胖小鼠血清高密度脂蛋白胆固醇浓度，因此KD比LFD干预对肥胖小鼠的减肥效果更有效，单纯饮食干预对肥胖小鼠骨骼肌脂代谢的影响不大；2． KH比LH有效降低小鼠Lee’s指数和体脂率，但导致甘油三酯和低密度脂蛋白胆固醇浓度升高；3．相同饮食干预下，HIIT比MICT有效增强小鼠骨骼肌脂代谢水平，主要通过增强AMPK-PGC-1α-PPARα介导的脂代谢通路实现。但相同运动干预下，KD和LFD结合运动干预对小鼠骨骼肌脂代谢水平影响的差别不大。
OBJECTIVE: To study the effects of different exercise combined diet interventions on weight loss and skeletal muscle lipid metabolism in nutritional obese mice, aiming to explore a healthy and effective exercise combined diet method for weight loss.METHODS: A total of 200 healthy male mice were treated with a high-fat diet for 8 weeks to establish a nutritional mouse obesity model. Obese mice (56 in total) were randomly divided into 7 groups: high-fat diet group (HFD), ketogenic diet group (KD), low-fat diet group (LFD), ketogenic diet plus high-intensity intermittent exercise group (KH), ketogenic diet plus moderate-intensity continuous training group (KM), low-fat diet plus high-intensity intermittent exercise group (LH), low-fat diet plus moderate-intensity continuous training group (LM). The duration of the intervention was 5 weeks and the exercise intervention was 6 days/week. At the end of the intervention, the mice were sacrificed and serum was taken for TC, TG, HDL-C, LDL-C, FFA, adiponectin and leptin. The viscera and subcutaneous fat tissue were weighed and paraffin sections were taken. The expression levels of pAMPK/AMPK, PGC-1α, PPARα, CPT-1 protein and Acadl, Acox1, CPT-1, Ehhadh and Mcad mRNA were measured by skeletal muscle.RESULTS: The ketogenic diet is effective in reducing the food intake and body fat rate of mice, and enhances the AMPK phosphorylation level and the fatty acid β oxidase Ehhadh gene expression level in mice skeletal muscle. The ketogenic diet combined with exercise effectively reduced the Lee’s index and body fat rate in mice compared to the low-fat diet. High-intensity interval training combined with dietary intervention was effective in reducing Lee’s index and body fat percentage in mice compared with moderate-intensity continuous training combined with dietary intervention. The ketogenic diet combined with exercise is more effective than low-fat diet combined with exercise to increase blood high-density lipoprotein cholesterol and lower triglyceride levels, but leads to an increase in low-density lipoprotein cholesterol. Under the intervention of ketogenic diet or low-fat diet, diet combined exercise intervention effectively increased the expression of protein genes related to fatty acid oxidation pathway in mice skeletal muscle than diet intervention alone. Under the intervention of ketogenic diet or low-fat diet, high-intensity interval training can effectively increase the expression of protein gene of mice skeletal muscle fatty acid oxidation pathway.CONCLUSIONS: 1. Five-week KD intervention and LFD intervention can improve obesity. KD is more effective than LFD in reducing body fat rate and increasing serum HDL-C concentration in obese mice. Therefore, KD is more effective than LFD intervention in reducing obese mice weight. Simple dietary intervention had little effect on skeletal muscle lipid metabolism in obese mice.2. KH decreased Lee's index and body fat rate more effectively than LH, but increased triglyceride and LDL cholesterol concentration.3. Under the same dietary intervention, HIIT can enhance the lipid metabolism of skeletal muscle more effectively than MICT, mainly through enhancing the lipid metabolism pathway mediated by AMPK-PGC-1α-PPARα. However, under the same exercise intervention, there was no significant difference between KD and LFD combined with exercise intervention on skeletal muscle lipid metabolism in mice.
