To investigate whether increasing tricarboxylic acid(TCA)cycle activity and ketogenic capacity would augment fatty acid(FA)oxidation induced by the peroxisome proliferator-activated receptor-alpha(PPARα)agonist clofi...To investigate whether increasing tricarboxylic acid(TCA)cycle activity and ketogenic capacity would augment fatty acid(FA)oxidation induced by the peroxisome proliferator-activated receptor-alpha(PPARα)agonist clofibrate,suckling newborn piglets(n=54)were assigned to 8 groups following a 2(±clofibrate)×4(glycerol succinate[SUC],triglycerides of 2-methylpentanoic acid[T2M],valeric acid[TC5]and hexanoic acid[TC6])factorial design.Each group was fed an isocaloric milk formula containing either 0%or 0.35%clofibrate(wt/wt,dry matter basis)with 5%SUC,T2M,TC5 or TC6 for 5 d.Another 6 pigs served as newborn controls.Fatty acid oxidation was examined in fresh homogenates of liver collected on d 6 using[1-^(14)C]palmitic acid(1 mM)as a substrate(0.265μCi/μmol).Measurements were performed in the absence or presence of L-carnitine(1 mM)or inhibitors of 3-hydroxy-3-methylglutaryl-CoA synthase(L659699,1.6μM)or acetoacetate-CoA deacylase(iodoacetamide,50μM).Without clofibrate stimulation,^(14)C accumulation in CO_(2) was higher from piglets fed diets containing T2M and TC5 than SUC,but similar to those fed TC6.Under clofibrate stimulation,accumulation also was higher in homogenates from piglets fed TC5 than all other dietary treatments.Interactions between clofibrate and carnitine or the inhibitors were observed(P=0.0004)for acid soluble products(ASP).In vitro addition of carnitine increased^(14)C-ASP(P<0.0001)above all other treatments,regardless of clofibrate treatment.The percentage of^(14)C in CO_(2) was higher(P=0.0023)in TC5 than in the control group.From these results we suggest that dietary supplementation of anaplerotic and ketogenic FA could impact FA oxidation and modify the metabolism of acetyl-CoA(product ofβ-oxidation)via alteration of TCA cycle activity,but the modification has no significant impact on the hepatic FA oxidative capacity induced by PPARα.In addition,the availability of carnitine is a critical element to maintain FA oxidation during the neonatal period.展开更多
The coconut tree(Cocos nucifera)which is also known as the“Tree of life”has its own values in each part of the tree and coconut oil is more prestigious among them.At present,the consumption of coconut oil is booming...The coconut tree(Cocos nucifera)which is also known as the“Tree of life”has its own values in each part of the tree and coconut oil is more prestigious among them.At present,the consumption of coconut oil is booming all around the world owing to its tremendous health benefits.The unique chemical composition of coconut oil enriched with medium chain fatty acids(MCFAs)has led to the exploration of these nutritional and therapeutic influences.Unlike the long chain fatty acids(LCFAs),the MCFAs generated from the digestion of medium chain triglycerides(MCTs)has a specific pathway for the metabolism,as it bypasses the lymphatic system and enter the liver directly through the portal vein.Due to such distinct attributes in absorption and metabolism,MCTs are readily capable of forming ketone bodies than other triglycerides.These ketone bodies are a competent energy source for the brains,especially those having cognitive impairments like Alzheimer's disease(AD).AD is a neurodegenerative disease characterized clinically by accelerating shortfalls in memory and behavioral changes.The principal biochemical hallmarks behind the pathogenesis of AD are the development of extracellular amyloidβplaques and the accumulation of intracellular neurofibrillary tangles.Occurrence of Cardiovascular diseases(CVD)with elevated LDL levels,hypertension,Type 2 diabetes,obesity,and insulin resistance are some key risk factors that are responsible for the increasing prevalence and incidence of AD.There is sufficient evidence to prove that MCTs in coconut oil are metabolized and absorbed in such a way that retards the severity of these physiological risk factors.Besides,coconut oil is endowed with many polyphenolic compounds that are serving as antioxidants by combating oxidative stress and inflammation,which in turn downregulates the etiology of AD.But depending on the different processing conditions applied in extraction techniques of coconut oil,variations in antioxidant capacity can take place.Even though there are inadequacies in peer-reviewed large cohort clinical data for the long run,this article reviews that coconut oil,its constituents,and metabolism have positive findings on the potentiality to treat AD as a nutritional supplement.展开更多
基金This work is supported by Animal Nutrition,Growth and Lactation(grant no.2015-67015-23245/project accession no.1005855)from the USDA National Institute of Food and Agriculturethe North Carolina Agricultural Research Hatch projects 1016618 and 02780。
文摘To investigate whether increasing tricarboxylic acid(TCA)cycle activity and ketogenic capacity would augment fatty acid(FA)oxidation induced by the peroxisome proliferator-activated receptor-alpha(PPARα)agonist clofibrate,suckling newborn piglets(n=54)were assigned to 8 groups following a 2(±clofibrate)×4(glycerol succinate[SUC],triglycerides of 2-methylpentanoic acid[T2M],valeric acid[TC5]and hexanoic acid[TC6])factorial design.Each group was fed an isocaloric milk formula containing either 0%or 0.35%clofibrate(wt/wt,dry matter basis)with 5%SUC,T2M,TC5 or TC6 for 5 d.Another 6 pigs served as newborn controls.Fatty acid oxidation was examined in fresh homogenates of liver collected on d 6 using[1-^(14)C]palmitic acid(1 mM)as a substrate(0.265μCi/μmol).Measurements were performed in the absence or presence of L-carnitine(1 mM)or inhibitors of 3-hydroxy-3-methylglutaryl-CoA synthase(L659699,1.6μM)or acetoacetate-CoA deacylase(iodoacetamide,50μM).Without clofibrate stimulation,^(14)C accumulation in CO_(2) was higher from piglets fed diets containing T2M and TC5 than SUC,but similar to those fed TC6.Under clofibrate stimulation,accumulation also was higher in homogenates from piglets fed TC5 than all other dietary treatments.Interactions between clofibrate and carnitine or the inhibitors were observed(P=0.0004)for acid soluble products(ASP).In vitro addition of carnitine increased^(14)C-ASP(P<0.0001)above all other treatments,regardless of clofibrate treatment.The percentage of^(14)C in CO_(2) was higher(P=0.0023)in TC5 than in the control group.From these results we suggest that dietary supplementation of anaplerotic and ketogenic FA could impact FA oxidation and modify the metabolism of acetyl-CoA(product ofβ-oxidation)via alteration of TCA cycle activity,but the modification has no significant impact on the hepatic FA oxidative capacity induced by PPARα.In addition,the availability of carnitine is a critical element to maintain FA oxidation during the neonatal period.
文摘The coconut tree(Cocos nucifera)which is also known as the“Tree of life”has its own values in each part of the tree and coconut oil is more prestigious among them.At present,the consumption of coconut oil is booming all around the world owing to its tremendous health benefits.The unique chemical composition of coconut oil enriched with medium chain fatty acids(MCFAs)has led to the exploration of these nutritional and therapeutic influences.Unlike the long chain fatty acids(LCFAs),the MCFAs generated from the digestion of medium chain triglycerides(MCTs)has a specific pathway for the metabolism,as it bypasses the lymphatic system and enter the liver directly through the portal vein.Due to such distinct attributes in absorption and metabolism,MCTs are readily capable of forming ketone bodies than other triglycerides.These ketone bodies are a competent energy source for the brains,especially those having cognitive impairments like Alzheimer's disease(AD).AD is a neurodegenerative disease characterized clinically by accelerating shortfalls in memory and behavioral changes.The principal biochemical hallmarks behind the pathogenesis of AD are the development of extracellular amyloidβplaques and the accumulation of intracellular neurofibrillary tangles.Occurrence of Cardiovascular diseases(CVD)with elevated LDL levels,hypertension,Type 2 diabetes,obesity,and insulin resistance are some key risk factors that are responsible for the increasing prevalence and incidence of AD.There is sufficient evidence to prove that MCTs in coconut oil are metabolized and absorbed in such a way that retards the severity of these physiological risk factors.Besides,coconut oil is endowed with many polyphenolic compounds that are serving as antioxidants by combating oxidative stress and inflammation,which in turn downregulates the etiology of AD.But depending on the different processing conditions applied in extraction techniques of coconut oil,variations in antioxidant capacity can take place.Even though there are inadequacies in peer-reviewed large cohort clinical data for the long run,this article reviews that coconut oil,its constituents,and metabolism have positive findings on the potentiality to treat AD as a nutritional supplement.