Effects Of Low-carbohydrate Diet And Ketogenic Diet On Glucose And Lipid Metabolism

With the prevalence of type 2 diabetes worldwide,it is urgent to find a suitable dietary intervention strategy.It has shown that ketogenic diet is effective in glycemic control,but there may be some side effects,such as hyperlipidemia and hepatic steatosis.Since the lowcarbohydrate diet contains less fat than ketogenic diet,it may be possible to ameliorate these side effects.However,the current research on the effects of the two diets on glucose and lipid metabolism in type 2 diabetic mice has not been unified yet.In the current study,we first established a model of type 2 diabetes in C57BL/6J mice with high-fat diet combined with streptozotocin,and then explored the effects of low-carbohydrate diet and ketogenic diet on glucose and lipid metabolism in liver and muscle of mice.First,the effect of diets on the overall metabolic characterization of mice was studied.Both the low-carbohydrate diet and ketogenic diet could reduce blood glucose,improve glucose tolerance and insulin sensitivity in type 2 diabetic mice,indicating that they were both beneficial for blood glucose control in diabetic mice.Secondly,we analyzed the effect of diets on glucose and lipid metabolism in liver of mice.In terms of glucose metabolism in liver,the glycogen content in low-carbohydrate diet group(18.76 mg/g)was higher than that in ketogenic diet group(4.89 mg/g),and the expression of gluconeogenesis related genes was significantly lower than that in ketogenic diet group,the mechanism of gluconeogenesis was further investigated,results indicated that lowcarbohydrate diet inhibited gluconeogenesis through AMP-activated kinase activation.With respect of lipid metabolism,the levels of liver damage markers alanine aminotransferase and aspartate aminotransferase(49.8 U/L,156.3 U/L)in the low-carbohydrate diet group were lower than those in the ketogenic diet group(110.9 U/L,213.9 U/L),suggesting that the lowcarbohydrate diet could improve liver damage in diabetic mice.At the same time,the ketogenic diet inhibited de novo lipogenesis and promoted lipid oxidation,so the ketogenic diet forced the body to use fatty acids for energy due to excessive fat supply.Finally,we studied the effect of diets on glucose and lipid metabolism in skeletal muscle of mice.The weight of skeletal muscle was analyzed,the weight of gastrocnemius and tibial anterior muscle(328.4 mg,205.8 mg)of the low-carbohydrate diet group was higher than those of the ketogenic diet group(301.5 mg,189.8 mg),and the expression of skeletal muscle atrophy marker genes was lower than in ketogenic diet group,results showed that low-carbohydrate diet could improve skeletal muscle atrophy.The expression levels of muscle fiber type marker genes and histochemical staining of skeletal muscle were determined,it was found that ketogenic diet promoted the transformation of muscle fiber from type ? to type ?,while low-carbohydrate diet maintained more type ?b muscle fiber content.In order to further explore the effect of muscle fiber transformation on metabolism of skeletal muscle,the expression of forkhead box O1(Fox O1),pyruvate dehydrogenase kinase 4(PDK4),phospho-pyruvate dehydrogenase(p-PDH)and pyruvate dehydrogenase complex(PDHC)activity were measured.The expression of Fox O1,PDK4 and p-PDH in low-carbohydrate diet group were lower than those in ketogenic diet group at m RNA and protein levels,and the PDHC activity was higher,so,low-carbohydrate diet promoted glucose utilization.With regard to lipid metabolism,the intramuscular triglyceride content of the ketogenic diet group(0.11 mmol/g)was higher than that of the lowcarbohydrate diet group(0.08 mmol/g),and it promoted skeletal muscle lipolysis,further indicating that mice in the ketogenic diet group were forced to use fatty acids for energy supply.In conclusion,both low-carbohydrate diet and ketogenic diet could reduce blood glucose,but their internal effects on the body were different.Low-carbohydrate diet inhibited hepatic gluconeogenesis,improved skeletal muscle atrophy and promoted glucose utilization in skeletal muscle,while ketogenic diet forced the body to use fatty acids for energy supply,activated hepatic gluconeogenesis and promoted lipolysis in skeletal muscle.Therefore,lowcarbohydrate diet may be more metabolically beneficial,and this study provides new insights into the selection of dietary intervention strategies for the treatment of type 2 diabetes mellitus.