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Chinese Medical Journal 2023年第11期136卷 1358-1360页

作者： Meng Chai Haitao Zhang Lixia Yang Jing Liang Hongya Han Xiaoli Liu Xiaoteng Ma Yan Liu Dongmei Shi Yingxin Zhao Yuyang Liu Yujie Zhou Department of Cardiology Beijing Anzhen HospitalCapital Medical UniversityBeijing Institute of Heart Lung and Blood Vessel DiseaseBeijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic DiseaseClinical Center for Coronary Heart DiseaseCapital Medical UniversityBeijing 100029China Department of Cardiology Air Force Medical CenterBeijing 100142China

Low-density lipoprotein cholesterol(LDL-C)is an independent risk factor for atherosclerotic cardiovascular disease(ASCVD).Even after lipid-lowering therapy(LLT)with statins or statin–ezetimibe,a large proportion of patients at very high risk still do not reach the LDL-C targets(<1.4 mmol/L and≥50%reduction).[1,2]Proprotein convertase subtilisin/kexin type 9 inhibitor(PCSK9i)is recommended for patients at high or very high cardiovascular risk inwhom LDL-C reduction is not adequate with statin therapy or in those with statin intolerance.Limited data are available regarding the use of PCSK9i in China.

关键词： patients lipid cardiovascular

lipid control in adult Chinese patients with type 2 diabetes:a retrospective analysis of time trends and geographic regional differences

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Chinese Medical Journal 2022年第3期135卷 356-358页

作者： Yanping Yuan Xianghai Zhou Juming Lu Xiaohui Guo Linong Ji Department of Endocrinology Peking University People's HospitalBeijing 100044China Department of Endocrinology Chinese PLA General HospitalBeijing 100853China Department of Endocrinology First Hospital of Peking UniversityBeijing 100034China

To the Editor:Patients with type 2 diabetes have a higher risk of cardiovascular diseases(CVD),relative to people without diabetes.Patients with diabetes always exhibit lipid abnormalities.Rapid economic development and accelerated urbanization have also led to lifestyle changes that may have an influence on the lipid parameters of Chinese patients with diabetes.Given the significant differences in socioeconomic status in China,geographical variations were also observed in the prevalence,awareness,treatment,and control of dyslipidemia among individuals who were≥45 years old in the general Chinese population.[1]There is a lack of large-scale studies regarding time trends and geographical variations in lipid concentrations and lipid control among Chinese adults with type 2 diabetes.Therefore,we conducted a study on time trends and geographical variations in lipid concentrations and lipid control in this population using the China National HbA1c Surveillance System(CNHSS)database of adult Chinese outpatients with type 2 diabetes during 2009 to 2013.The Ethics Committee of the Chinese People Liberation Army General Hospital approved the study protocol.Informed consent was obtained from all the patients before they were interviewed and data collected.

关键词： patients diabetes lipid

lipid catabolism and mitochondrial uncoupling are stimulated in brown adipose tissue of amyotrophic lateral sclerosis mouse models

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Genes & Diseases 2023年第2期10卷 321-324页

作者： Fabio Ciccarone Serena Castelli Giacomo Lazzarino Silvia Scaricamazza Renata Mangione Sergio Bernardini Savina Apolloni Nadia D'Ambrosi Alberto Ferri Maria Rosa Ciriolo Department of Biology University of Rome “Tor Vergata”00133 RomeItaly IRCCS San Raffaele Roma 00166 RomeItaly UniCamillus-Saint Camillus International University of Health Sciences 00131 RomeItaly IRCCS Fondazione Santa Lucia 00179 RomeItaly Department of Basic Biotechnological Sciences Intensive and Perioperative ClinicsCatholic University of Rome00168 RomeItaly Fondazione Policlinico Universitario A. Gemelli IRCCS 00168 RomeItaly Institute of Translational Pharmacology IFT-CNR 00133 RomeItaly

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease typically leading to death within 5 years from symptom onset. ALS familial forms are associated with mutations in several genes, including Superoxide Dismutase 1 (SOD1) and Fused in Sarcoma (FUS). Although genes linked to ALS participate in disparate biological processes, ALS genetic variants largely trigger shared pathogenic events such as oxidative stress, protein aggregation and defects in RNA processing. Moreover, ALS patients show systemic hypermetabolism that leads to increased energy expenditure at rest and thus weight loss during the disease course.1 ALS hypermetabolic phenotype and weight loss have been extensively characterized in mice bearing the G93A substitution in SOD1 protein (SOD1-G93A), which exhibit skeletal-muscle metabolic reprogramming before disease onset.

关键词： lipid metabolism aggregation

ORP8 acts as a lipophagy receptor to mediate lipid droplet turnover

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Protein & Cell 2023年第9期14卷 653-667页

作者： Maomao Pu Wenhui Zheng Hongtao Zhang Wei Wan Chao Peng Xuebo Chen Xinchang Liu Zizhen Xu Tianhua Zhou Qiming Sun Dante Neculai Wei Liu Metabolic Medicine Center International Institutes of Medicinethe Fourth Affiliated HospitalZhejiang University School of MedicineYiwu 322000China Joint Institute of Genetics and Genomics Medicine between Zhejiang University and University of Toronto Hangzhou 310058China National Center for Protein Science Shanghai Institute of Biochemistry and Cell BiologyShanghai Institutes of Biological SciencesChinese Academy of SciencesShanghai200031China

Lipophagy,the selective engulfment of lipid droplets(LDs)by autophagosomes for lysosomal degradation,is critical to lipid and energy homeostasis.Here we show that the lipid transfer protein ORP8 is located on LDs and mediates the encapsulation of LDs by autophagosomal membranes.This function of oRP8 is independent of its lipid transporter activity and is achieved through direct interaction with phagophore-anchored LC3/GABARAPs.Upon lipophagy induction,ORP8 has increased localization on LDs and is phosphorylated by AMPK,thereby enhancing its affinity for LC3/GABARAPs.Deletion of ORP8 or interruption of ORP8-LC3/GABARAP interaction results in accumulation of LDs and increased intracellular triglyceride.Overexpression of ORP8 alleviates LD and triglyceride deposition in the liver of ob/ob mice,and Osbpl8 mice exhibit liver lipid clearance defects.Our results suggest that ORP8 is a lipophagy receptor that plays a key role in cellular lipid metabolism.

关键词： ORP8 lipophagy lipid autophagy

Developmental changes in lipid and fatty acid metabolism and the inhibition by in ovo feeding oleic acid in Muscovy duck embryogenesis

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Animal Nutrition 2023年第1期12卷 321-333页

作者： Xiufen Zhang Qilin Wu Wenxuan Zheng Chuang Liu Liang Huang Xin Zuo Wenquan Xiao Xiaofeng Han Hui Ye Wence Wang Lin Yang Yongwen Zhu Guangdong Provincial Key Laboratory of Animal Nutrition and Regulation College of Animal ScienceSouth China Agricultural UniversityGuangzhou 510642China Wen's Food Group Co. LtdYunfu 52740China

Hepatic lipid and fatty acid(FA)metabolism are critical for regulating energetic homeostasis during embryogenesis.At present,it remains unclear how an exogenous FA intervention affects embryonic development in an avian embryo model.In Exp.1,30 fertilized eggs were sampled on embryonic days(E)16,19,22,25,28,31 and the day of hatch(DOH)to determine the critical period of lipid metabolism.In Exp.2,a total of 120 fertilized eggs were divided into two groups(60 eggs/group)for in ovo feeding(IOF)procedures on E25.Eggs were injected into the yolk sac with PBS as the control group and with oleic acid(OA)as the IOF-OA treatment group.Samples were collected on E28 and E31.In Exp.1,hepatic triacylglycerol(TG)and cholesterol(CHO)contents increased while serum TG content decreased from E16 to DOH(P0.05).Maximal metabolic changes in lipid and FA metabolism occurred on E22-E28 in Muscovy duck embryogenesis,along with the altered target gene and protein expression related to lipogenesis and lipolysis.IOF-OA intervention on E25 could inhibit the target gene expression related to FA uptake,synthesis,and oxidation,which may influence the normal FA metabolism on E28 during embryogenesis.

关键词： Embryo lipid Triacylglycerol Cholesterol Fatty acid Oleic acid

The effects of prey lipid on female mating and reproduction of a wolf spider

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Current Zoology 2022年第6期68卷 726-733页

作者： Qingguo FENG Lelei WEN Jiayi MA Long YU Changchun LI Xiaoguo JIAO State Key Laboratory of Biocatalysis and Enzyme Engineering Center for Behavioral Ecology and EvolutionSchool of Life SciencesHubei UniversityWuhan 430062China Hubei Key Laboratory of Quality Control of Characteristic Fruits and Vegetables College of Life Science and TechnologyHubei Engineering UniversityXiaogan 432000China

As predators,the macronutrients spiders extract from their prey play important roles in their mating and reproduction.Previous studies of macronutrients on spider mating and reproduction focus on protein,the potential impact of prey lipid content on spider mating and reproduction remains largely unexplored.Here,we tested the influence of prey varying in lipid content on female mating,sexual cannibalism,reproduction,and offspring fitness in the wolf spider Pardosa pseudoannulata.We acquired 2 groups of fruit fly Drosophila melanogaster that differed significantly in lipid but not protein content by supplementing cultural media with a high or low dose of sucrose on which the fruit flies were reared(HL:high lipid and LL:low lipid).Subadult(i.e.,1 molt before adult)female spiders that fed HL flies matured with significantly higher lipid content than those fed LL flies.We found that the mated females fed with HL flies significantly shortened pre-oviposition time and resulted in a significantly higher fecundity.However,there was no significant difference in female spiders varying in lipid content on other behaviors and traits,including the latency to courtship,courtship duration,mating,copulation duration,sexual cannibalism,offspring body size,and survival.Hence,our results suggest that the lipid content of prey may be a limiting factor for female reproduction,but not for other behavioral traits in the wolf spiders P.pseudoannulata.

关键词： lipid mating macronutrients Pardosa pseudoannulata reproduction survival

Fibroblast growth factor 21(FGF21) attenuates tacrolimus-induced hepatic lipid accumulation through transcription factor EB(TFEB)-regulated lipophagy

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第6期24卷 485-495页

作者： Zhensheng ZHANG Li XU Xun QIU Xinyu YANG Zhengxing LIAN Xuyong WEI Di LU Xiao XU Zhejiang University School of Medicine Hangzhou 310058China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Hangzhou 310006China Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Institute of Organ Transplantation Zhejiang UniversityHangzhou 310003China NHC Key Laboratory of Combined Multi-organ Transplantation Hangzhou 310003China Westlake Laboratory of Life Sciences and Biomedicine Hangzhou 310024China

Tacrolimus(TAC),also called FK506,is one of the classical immunosuppressants to prevent allograft rejection after liver transplantation.However,it has been proved to be associated with post-transplant hyperlipemia.The mechanism behind this is unknown,and it is urgent to explore preventive strategies for hyperlipemia after transplantation.Therefore,we established a hyperlipemia mouse model to investigate the mechanism,by injecting TAC intraperitoneally for eight weeks.After TAC treatment,the mice developed hyperlipemia(manifested as elevated triglyceride(TG)and low-density lipoprotein cholesterol(LDL-c),as well as decreased high-density lipoprotein cholesterol(HDL-c)).Accumulation of lipid droplets was observed in the liver.In addition to lipid accumulation,TAC induced inhibition of the autophagy-lysosome pathway(microtubule-associated protein 1light chain 3β(LC3B)II/I and LC3B II/actin ratios,transcription factor EB(TFEB),protein 62(P62),and lysosomal-associated membrane protein 1(LAMP1))and downregulation of fibroblast growth factor 21(FGF21)in vivo.Overexpression of FGF21may reverse TAC-induced TG accumulation.In this mouse model,the recombinant FGF21 protein ameliorated hepatic lipid accumulation and hyperlipemia through repair of the autophagy-lysosome pathway.We conclude that TAC downregulates FGF21and thus exacerbates lipid accumulation by impairing the autophagy-lysosome pathway.Recombinant FGF21 protein treatment could therefore reverse TAC-caused lipid accumulation and hypertriglyceridemia by enhancing autophagy.

关键词： Autophagy Fibroblast growth factor 21(FGF21) lipid Lipophagy Lysosome Tacrolimus Transcription factor EB(TFEB)

Melanin precursors mediated adaption to temperature changes in fungus and animal via inhibition of lipid-mediated ferroptosis

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Science China(Life Sciences) 2023年第8期66卷 1800-1817页

作者： Xiaoyu Yang Yonghong Chen Longlong Zhang Jiangbo He Qunfu Wu Shuhong Li Donglou Wang Jianghui Gou Zhuang Wu Keqin Zhang Shenghong Li Xuemei Niu State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan and Key Laboratory for Southwest Microbial Diversity of the Ministry of EducationYunnan UniversityKunming 650032China State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of BotanyChinese Academy of SciencesKunming 650201China Kunming Key Laboratory of Respiratory Disease Kunming UniversityKunming 650214China

The discovery of biological activities of natural products plays a vital part in drug development.The mechanism by which organisms respond to temperature changes via biosynthesis of natural products remained largely cryptic.A thermophilic fungus under cold stress turned black and accumulated a polyketide metabolite 1 and lipid mass.Deficiency in 1 caused melanin loss and accumulated extra lipid mass,unexpectedly leading to seriously damaged mitochondria diagnostic for ferroptosis.Further analysis revealed that lipid mass induced by cold stress intensively increased ferroptosis risk and 1 functioned as cell wall reinforcer against mass lipid accumulation and as reactive oxygen species scavenger against lipid peroxidation.We also found that melanin in mice lowered lipid level but enhanced animal resistance to cold stress.Treatment with melanin precursors significantly increased mouse cell survival rate under cold stress.Our results unveiled a metabolite-lipid-ferroptosis-cold relationship,which provided mechanistic insights into the functions of most common metabolites and into diseases related to cold stress.These findings opened a perspective for developing anti-cold and anti-ferroptosis therapeutics and agents.

关键词： melanin precursor lipid ferroptosis temperature change anti-cold

Polymorphisms of the Vitamin D Receptor Gene and SexDifferential Associations with lipid Profiles in Chinese Han Adults

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Biomedical and Environmental Sciences 2022年第2期35卷 115-125页

作者： CHEN Yan Mei XU Ping WANG Zhou Tian ZHU Yu Mei GONG Chun Mei HUANG Chang Hua LIU Xiao Li ZHOU Ji Chang School of Public Health(Shenzhen) Sun Yat-sen UniversityShenzhen 518100GuangdongChina Shenzhen Center for Chronic Disease Control Shenzhen 518020GuangdongChina Shenzhen Qilinshan Sanatorium Shenzhen 518055GuangdongChina Guangdong Province Engineering Laboratory for Nutrition Translation Guangzhou 510080GuangdongChina

Objective To explore the association of single nucleotide polymorphisms(SNPs)of the vitamin D receptor gene(VDR)with circulating lipids considering gender differences.Methods Of the Han Chinese adults recruited from a health examination center for inclusion in the study,the circulating lipids,25-hydroxyvitamin D(25OHD),and other parameters were measured.The VDR SNPs of Cdx2(rs11568820),Fok1(rs2228570),Apa1(rs7975232),and Taq1(rs731236)were genotyped with a qPCR test using blood DNA samples,and their associations with lipids were analyzed using logistic regression.Results In the female participants(n=236 with dyslipidemia and 888 without dyslipidemia),multiple genotype models of Fok1 indicated a positive correlation of B(not A)alleles with LDLC level(Plipidemia and 564 without dyslipidemia),the recessive model of Cdx2 and the additive and recessive models of Fok1 differed(P<0.05)between the HDLC-classified subgroups,respectively,and Fok1 BB and Cdx2 TT presented interactions with 25OHD in the negative associations with HDLC(P<0.05).Conclusion In the Chinese Han adults included in the study,the Fok1 B-allele of VDR was associated with higher LDLC in females,and the Fok1 B-allele and the Cdx2 T-allele of VDR were associated with lower HDLC in males.The interaction of VD and Fok1 BB or Cdx2 TT in males synergistically decreased HDLC levels.

关键词： Vitamin D Vitamin D receptor Gene polymorphism lipid Dyslipidemia

The role of lipids in fermentative propionate production from the co-fermentation of lipid and food waste

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Frontiers of Environmental Science & Engineering 2023年第7期17卷 107-118页

作者： Niyou Xu Ting Chen Jun Yin School of Environmental Science and Engineering Zhejiang Gongshang UniversityHangzhou 310012China Zhejiang Provincial Key Laboratory of Solid Waste Treatment and Recycling Hangzhou 310012China

Food waste(FW)is a promising renewable low-cost biomass substrate for enhancing the economic feasibility of fermentative propionate production.Although lipids,a common component of food waste,can be used as a carbon source to enhance the production of volatile fatty acids(VFAs)during co-fermentation,few studies have evaluated the potential for directional propionate production from the co-fermentation of lipids and FW.In this study,co-fermentation experiments were conducted using different combinations of lipids and FW for VFA production.The contributions of lipids and FW to propionate production,hydrolysis of substrates,and microbial composition during.cofermentation were evaluated.The results revealed that lipids shifted the fermentation type of FW from butyric to propionic acid fermentation.Based on the estimated propionate production kinetic parameters,the maximum propionate productivity increased significantly with an increase in lipid content,reaching 6.23 g propionate/(L·d)at a lipid content of 50%.Propionate-producing bacteria Prevotella,Veillonella,and norank f Propionibacteriaceae were enriched in the presence of lipids,and the succinate pathway was identified as a prominent fermentation route for propionate production.Moreover,the Kyoto Encyclopedia of Genes and Genomes functional annotation revealed that the expression of functional genes associated with amino acid metabolism was enhanced by the presence of lipids.Collectively,these findings will contribute to gaining a better understanding of targeted propionate production from FW.

关键词： Acidogenic fermentation Microbial community Volatile fatty acid Propionate Foodwaste lipid