Activation of mitochondrial function and heat production in adipose tissue by the modification of dietary fat is a promising strategy against obesity.However,as an important source of lipids for ketogenic and daily di...Activation of mitochondrial function and heat production in adipose tissue by the modification of dietary fat is a promising strategy against obesity.However,as an important source of lipids for ketogenic and daily diets,the function of fats extracted from different adipose tissue sites was largely unknown.In this study,we illustrated the function of fats extracted from adipose tissues with different"beigeing"properties in the ketogenic diet and identified lipid profiles of fats that facilitate energy expenditure.We found that the anti-obesity effect of ketogenic diets was potentiated by using"beigeing"fat[porcine subcutaneous adipose tissue(SAT)]as a major energy-providing ingredient.Through lipidomic analyses,phosphatidylserine(PS)was identified as a functional lipid activating thermogenesis in adipose tissue.Moreover,in vivo studies showed that PS induces adipose tissue thermogenesis and alleviates diet-induced obesity in mice.Invitro studies showed that PS promotes UCP1 expression and lipolysis of adipocytes.Mechanistically,PS promoted mitochondrial function in adipocytes via the ADCY3-cAMP-PKA-PGClαpathway.In addition,PS-PGCla binding may affect the stability of the PGClαprotein,which further augments PS-induced thermogenesis.These results demonstrated the efficacy of dietary SAT fats in diminishing lipid accumulation and the underlying molecular mechanism of PS in enhancing UCP1 expression and mitochondrial function.Thus,our findings suggest that as dietary fat,"beigeing"fat provides more beneficial lipids that contribute to the improvement of mitochondrial function,including PS,which may become a novel,nonpharmacological therapy to increase energy expenditure and counteract obesity and its related diseases.展开更多
基金supported by the National Natural Science Foundation of China(32272887 and 31722053)the National Key R&D Program of China(2018YFA0800403)to T.S.
文摘Activation of mitochondrial function and heat production in adipose tissue by the modification of dietary fat is a promising strategy against obesity.However,as an important source of lipids for ketogenic and daily diets,the function of fats extracted from different adipose tissue sites was largely unknown.In this study,we illustrated the function of fats extracted from adipose tissues with different"beigeing"properties in the ketogenic diet and identified lipid profiles of fats that facilitate energy expenditure.We found that the anti-obesity effect of ketogenic diets was potentiated by using"beigeing"fat[porcine subcutaneous adipose tissue(SAT)]as a major energy-providing ingredient.Through lipidomic analyses,phosphatidylserine(PS)was identified as a functional lipid activating thermogenesis in adipose tissue.Moreover,in vivo studies showed that PS induces adipose tissue thermogenesis and alleviates diet-induced obesity in mice.Invitro studies showed that PS promotes UCP1 expression and lipolysis of adipocytes.Mechanistically,PS promoted mitochondrial function in adipocytes via the ADCY3-cAMP-PKA-PGClαpathway.In addition,PS-PGCla binding may affect the stability of the PGClαprotein,which further augments PS-induced thermogenesis.These results demonstrated the efficacy of dietary SAT fats in diminishing lipid accumulation and the underlying molecular mechanism of PS in enhancing UCP1 expression and mitochondrial function.Thus,our findings suggest that as dietary fat,"beigeing"fat provides more beneficial lipids that contribute to the improvement of mitochondrial function,including PS,which may become a novel,nonpharmacological therapy to increase energy expenditure and counteract obesity and its related diseases.
