OBJECTIVE:To explore whether kidney Yang deficiency(KYD)is prone to metabolic disorders may be linked to impaired mitochondrial function in thermogenesis and metabolic tissues.METHODS:A rat model of KYD was used,which...OBJECTIVE:To explore whether kidney Yang deficiency(KYD)is prone to metabolic disorders may be linked to impaired mitochondrial function in thermogenesis and metabolic tissues.METHODS:A rat model of KYD was used,which was established using Sprague Dawley rat dams with warm preference subjected to herbal treatment that can improve kidney Yang.The human relevance was confirmed by reduced serum corticosterone levels,and increased preference for warm location.RESULTS:KYD Rats were underdeveloped.Adenosinetriphosphate(ATP)production was reduced in the brown fat,but increased in the muscle.However,oxidative phosphorylated complexes to generate ATP and mitochondrial biogenesis marker were reduced in both tissues.When the second insult of high-fat diet(HFD)was introduced,KYD rats gained less weight yet developed more severe lipid and glucose metabolic disorders.This may be driven by disregulated liver gluconeogenesis marker forkhead box protein O1 and lipid metabolic regulator cholesterol 7 alpha-hydroxylase.CONCLUSION:KYD rats exhibited reduced mitochondrial function in the brown fat,but were partially compensated by skeletal muscle,associated with the phenotype of warm preference and metabolic disorder,which was further exacerbated by additional HFD consumption.Future studies can focus on treatment targetting mitochondria function to reverse this phenotype.展开更多
基金Supported by International Young Scientist Fellowship:the Role of Mitochondrial Intergrity in the Pathophysiology of Kidney Yang Deficiency(No.81750110554)National Natural Science Foundation of China:Central Mechanisms of Transgenerational Phenotype of Kidney Yang Deficiency in a Rat Model(No.2018HH0085)+2 种基金National Natural Science Foundation of China:Molecular Mechanism of Blocking Cys259 and DD-mediated p75NTR Signaling Pathway to Delay the Progression of Alzheimer’s Disease(NSFC 81971309)Guangdong Basic and Applied Basic Research Foundation:Mechanism Study of Cys259 Site and DD Domain of p75NTR as New Targets for the Treatment of Alzheimer’s Disease(2019A1515011333)Sun Yat-sen University Key Training Program for Youth Teachers:Research on Glial Connexin as a New Target for Alzheimer’s Disease Treatment(F7201931620002)。
文摘OBJECTIVE:To explore whether kidney Yang deficiency(KYD)is prone to metabolic disorders may be linked to impaired mitochondrial function in thermogenesis and metabolic tissues.METHODS:A rat model of KYD was used,which was established using Sprague Dawley rat dams with warm preference subjected to herbal treatment that can improve kidney Yang.The human relevance was confirmed by reduced serum corticosterone levels,and increased preference for warm location.RESULTS:KYD Rats were underdeveloped.Adenosinetriphosphate(ATP)production was reduced in the brown fat,but increased in the muscle.However,oxidative phosphorylated complexes to generate ATP and mitochondrial biogenesis marker were reduced in both tissues.When the second insult of high-fat diet(HFD)was introduced,KYD rats gained less weight yet developed more severe lipid and glucose metabolic disorders.This may be driven by disregulated liver gluconeogenesis marker forkhead box protein O1 and lipid metabolic regulator cholesterol 7 alpha-hydroxylase.CONCLUSION:KYD rats exhibited reduced mitochondrial function in the brown fat,but were partially compensated by skeletal muscle,associated with the phenotype of warm preference and metabolic disorder,which was further exacerbated by additional HFD consumption.Future studies can focus on treatment targetting mitochondria function to reverse this phenotype.