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Exercise during weight loss improves hepatic mitophagy

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Sports Medicine and Health Science 2022年第3期4卷 183-189页

作者： Megan E.Rosa-Caldwell Kaylee E.Poole Andrew Seija Matthew P.Harris Nicholas P.Greene Joshua S.Wooten Cacheixia Research Laboratory Exercise Science Research CenterDepartment of HealthHuman Performanceand RecreationUniversity of ArkansasFayettevilleARUSA Department of Neurology Beth Israel Deaconess Medical CenterBostonMAUSA Department of Applied Health Southern Illinois University EdwardsvilleEdwardsvilleILUSA

Non-alcoholic fatty liver disease(NAFLD)has recently become a public health concern concurrent with the obesity crisis.Previous work has shown aberrant mitochondrial content/quality and autophagy in models of NAFLD,whereas exercise is known to improve these derangements.The purpose of this study was to examine the effect of different weight-loss modalities on hepatic mitochondrial content,autophagy and mitophagy in NAFLD.Forty-eight male C57BL/6J mice were divided into 1 of 4 groups:low fat diet(LFD,10%fat,18 weeks),high fat diet(HFD,60%fat diet,18 weeks),weight-loss by diet(D,60%fat diet for 10 weeks then 10%fat diet for 8 weeks)or weight-loss by diet and physical activity(D/PA,60%fat diet for 10 weeks,then 10%fat diet plus a running wheel for 8 weeks).Immunoblot data were analyzed by one-way analysis of variance(ANOVA)with significance denoted at phepatic mitochondrial quality above control values.

关键词： Autophagy High-fat diet Mitochondria hepatic metabolism

Integrated liver proteomics and metabolomics identify metabolic pathways affected by pantothenic acid deficiency in Pekin ducks

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Animal Nutrition 2022年第4期11卷 1-14页

作者： Jing Tang Yongbao Wu Bo Zhang Suyun Liang Zhanbao Guo Jian Hu Zhengkui Zhou Ming Xie Shuisheng Hou State Key Laboratory of Animal Nutrition Key Laboratory of Animal(Poultry)Genetics Breeding and ReproductionMinistry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural Sciences100193BeijingChina

Pantothenic acid deficiency(PAD)in animals causes growth depression,fasting hypoglycemia and impaired lipid and glucose metabolism.However,a systematic multi-omics analysis of effects of PAD on hepatic function has apparently not been reported.We investigated liver proteome and metabolome changes induced by PAD to explain its effects on growth and liver metabolic disorders.Pekin ducks(1-dold,n=128)were allocated into 2 groups,with 8 replicates and 8 birds per replicate.For 16 d,all ducks had ad libitum access to either a PAD or a pantothenic acid adequate(control,CON)diet,formulated by supplementing a basal diet with 0 or 8 mg pantothenic acid/kg of diet,respectively.Liver enlargement,elevated liver glycogen concentrations and decreased liver concentrations of triglyceride and unsaturated fatty acids were present in the PAD group compared to the CON group.Based on integrated liver proteomics and metabolomics,PAD mainly affected glycogen synthesis and degradation,glycolysis and gluconeogenesis,tricarboxylic acid(TCA)cycle,peroxisome proliferator-activated receptor(PPAR)signaling pathway,fatty acid beta oxidation,and oxidative phosphorylation.Selected proteins were confirmed by Western blotting.Downregulation of proteins and metabolites involved in glycogen synthesis and degradation,glycolysis and gluconeogenesis implied that these processes were impaired in PAD ducks,which could have contributed to fasting hypoglycemia,liver glycogen storage,insufficient ATP production,and growth retardation.In contrast,PAD also upregulated proteins and metabolites involved in fatty acid beta oxidation,the TCA cycle,and oxidative phosphorylation processes in the liver;presumably compensatory responses to produce ATP.We inferred that PAD decreased liver triglyceride and unsaturated fatty acids by activating fatty acid beta oxidation and impairing unsaturated fatty acid synthesis.These findings contributed to our understanding of the mechanisms of PAD-induced changes in hepatic metabolism.

关键词： Pantothenic acid hepatic metabolism Proteomics Metabolomics Hypoglycemia

Selenogenome and AMPK signal insight into the protective effect of dietary selenium on chronic heat stress-induced hepatic metabolic disorder in growing pigs

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Journal of Animal Science and Biotechnology 2022年第1期13卷 152-165页

作者： Yan Liu Jiayong Tang Ying He Gang Jia Guangmang Liu Gang Tian Xiaoling Chen Jingyi Cai Bo Kang Hua Zhao Animal Nutrition Institute Sichuan Agricultural UniversityChengdu 611130SichuanChina Key Laboratory for Animal Disease-Resistance Nutrition Ministry of EducationHuimin RoadWenjiang DistrictChengdu 611130SichuanChina College of Animal Science and Technology Sichuan Agricultural UniversityChengdu 611130SichuanChina

Background:Chronic heat stress(CHS)disrupts hepatic metabolic homeostasis and jeopardizes product quality of pigs.Selenium(Se)may regulate the metabolic state through affect selenoprotein.Thus,we investigate the protective effect of dietary hydroxy-4-methylselenobutanoic acid(HMSeBA)on CHS induced hepatic metabolic disorder in growing pigs,and the corresponding response of selenoprotein.Methods:Forty crossbreed growing pigs were randomly assigned to five groups:control group raised in the thermoneutral environment(22±2℃)with basal diet;four CHS groups raised in hyperthermal condition(33±2℃)with basal diet and supplied with 0.0,0.2,0.4,and 0.6 mg Se/kg HMSeBA,respectively.The trial lasted 28 d.The serum biochemical,hepatic metabolism related enzyme,protein and gene expression and 25 selenoproteins in liver tissue were determined by real-time PCR,ELISA and western blot.Results:CHS significantly increased the rectal temperature,respiration rate,serum aspartate aminotransferase(AST)and low-density lipoprotein cholesterol(LDL-C)of pigs,up-regulated hepatic heat shock protein 70(HSP70)and induced lower liver weight,glycogen content,hepatic glucokinase and glutathione peroxidase(GSH-Px).The CHSinduced liver metabolic disorder was associated with the aberrant expression of 6 metabolism-related gene and 11 selenoprotein encoding genes,and decreased the protein abundance of GCK,GPX4 and SELENOS.HMSeBA improved anti-oxidative capacity of liver.0.4 or 0.6 mg Se/kg HMSeBA supplementation recovered the liver weight,glycogen content and rescue of mRNA abundance of genes related to metabolism and protein levels of GCK.HMSeBA supplementation changed expressions of 15 selenoprotein encoding genes,and enhanced protein expression of GPX1,GPX4 and SELENOS in the liver affected by CHS.CHS alone showed no impact while HMSeBA supplementation increased protein levels of p-AMPKαin the liver.Conclusions:In summary,HMSeBA supplementation beyond nutrient requirement mitigates CHS-induced hepatic metabolic disorder,recovered the liver glycoge

关键词： Chronic heat stress hepatic metabolism HMSeBA Pigs Selenoprotein

Highly expressed BMP9/GDF2 in postnatal mouse liver and lungs may account for its pleiotropic effects on stem cell differentiation,angiogenesis,tumor growth and metabolism

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Genes & Diseases 2020年第2期7卷 235-244页

作者： Wei Liu Zhongliang Deng Zongyue Zeng Jiaming Fan Yixiao Feng Xi Wang Daigui Cao Bo Zhang Lijuan Yang Bin Liu Mikhail Pakvasa William Wagstaff Xiaoxing Wu Huaxiu Luo Jing Zhang Meng Zhang Fang He Yukun Mao Huiming Ding Yongtao Zhang Changchun Niu Rex C.Haydon Hue H.Luu Jennifer Moriatis Wolf Michael J.Lee Wei Huang Tong-Chuan He Yulong Zou Departments of Orthopedic Surgery Breast SurgeryGastrointestinal SurgeryObstetrics and Gynecologyand NephrologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Orthopaedic Surgery The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China Ministry of Education Key Laboratory of Diagnostic Medicine The School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Laboratory Diagnostic Medicine Chongqing General HospitalChongqing 400021China Key Laboratory of Orthopaedic Surgery of Gansu Province The Departments of Orthopaedic Surgery and Obstetrics and GynecologyThe First and Second Hospitals of Lanzhou UniversityLanzhou730030China School of Life Sciences Southwest UniversityChongqing 400715China Department of Burn and Plastic Surgery West China Hospital of Sichuan UniversityChengdu 610041China Department of Orthopaedic Surgery The First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405China Department of Orthopaedic Surgery The Affiliated Zhongnan Hospital of Wuhan UniversityWuhan 430072China Department of Orthopaedic Surgery BenQ Medical Center Affiliated with Nanjing Medical UniversityNanjing 210000China Department of Orthopaedic Surgery The Affiliated Hospital of Qingdao UniversityQingdao 266061China

Bone morphogenetic protein 9(BMP9)(or GDF2)was originally identified from fetal mouse liver cDNA libraries.Emerging evidence indicates BMP9 exerts diverse and pleiotropic functions during postnatal development and in maintaining tissue homeostasis.However,the expression landscape of BMP9 signaling during development and/or in adult tissues remains to be analyzed.Here,we conducted a comprehensive analysis of the expression landscape of BMP9 and its signaling mediators in postnatal mice.By analyzing mouse ENCODE transcriptome datasets we found Bmp9 was highly expressed in the liver and detectable in embryonic brain,adult lungs and adult placenta.We next conducted a comprehensive qPCR analysis of RNAs isolated from major mouse tissues/organs at various ages.We found that Bmp9 was highly expressed in the liver and lung tissues of young adult mice,but decreased in older mice.Interestingly,Bmp9 was only expressed at low to modest levels in developing bones.BMP9-associated TGFβ/BMPR type I receptor Alk1 was highly expressed in the adult lungs.Furthermore,the feedback inhibitor Smads Smad6 and Smad7 were widely expressed in mouse postnatal tissues.However,the BMP signaling antagonist noggin was highly expressed in fat and heart in the older age groups,as well as in kidney,liver and lungs in a biphasic fashion.Thus,our findings indicate that the circulating BMP9 produced in liver and lungs may account for its pleiotropic effects on postnatal tissues/organs although possible roles of BMP9 signaling in liver and lungs remain to be fully understood.

关键词： BMP9/GDF2 Bone morphogenetic proteins(BMPs) hepatic metabolism Mesenchymal stem cells Neurogenesis Osteogenic differentiation Pulmonary arterial hypertension Tumorigenesis

Dynamic carbon 13 breath tests for the study of liver function and gastric emptying

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Gastroenterology Report 2015年第1期3卷 12-21页

作者： Leonilde Bonfrate Ignazio Grattagliano Giuseppe Palasciano Piero Portincasa Department of Biomedical Sciences and Human Oncology Clinica Medica‘A.Murri’University of Bari Medical SchoolBariItaly Italian College of General Practitioners Florence and BariItaly

In gastroenterological practice,breath tests(BTs)are diagnostic tools used for indirect,non-invasive assessment of several pathophysiological metabolic processes,by monitoring the appearance in breath of a metabolite of a specific substrate.Labelled substrates originally employed radioactive carbon 14(^(14)C)and,more recently,the stable carbon 13 isotope(^(13)C)has been introduced to label specific substrates.The ingested^(13)C-substrate is metabolized,and exhaled^(13)CO_(2)is measured by mass spectrometry or infrared spectroscopy.Some^(13)C-BTs evaluate specific(microsomal,cytosolic,and mitochondrial)hepatic metabolic pathways and can be employed in liver diseases(i.***.simple liver steatosis,non-alcoholic steato-hepatitis,liver fibrosis,cirrhosis,hepatocellular carcinoma,drug and alcohol effects).Another field of clinical application for^(13)C-BTs is the assessment of gastric emptying kinetics in response to liquids(^(13)C-acetate)or solids(^(13)C-octanoic acid in egg yolk or in a pre-packed muffin or the^(13)C-Spirulina platensis given with a meal or a biscuit).Studies have shown that^(13)C-BTs,used for gastric emptying studies,yield results that are comparable to scintigraphy and can be useful in detecting either delayed-(gastroparesis)or accelerated gastric emptying or changes of gastric kinetics due to pharmacological effects.Thus,^(13)C-BTs represent an indirect,cost-effective and easy method of evaluating dynamic liver function and gastric kinetics in health and disease,and several other potential applications are being studied.

关键词： breath tests stable isotope hepatic metabolism gastric motility scintigraphy

Glucuronidation is the dominating in-vivo metabolism pathway of herbacetin:elucidation of herbacetin pharmacokinetics after intravenous and oral administration in rats

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中国药理学与毒理学杂志 2017年第10期31卷 1019-1019页

作者： Bei-kang GE Liang ZHAO Te QI Ping-xiang XU Ming XUE Department of Pharmacology School of Basic Medical SciencesCapital Medical University

OBJECTIVE To map a comprehensive metabolic pathway of herbacetin in rats,specifically,to elucidate the biotransformation of herbacetin in vivo and to simultaneously monitor the pharmacokinetic process of both parent drug and its major metabolites.METHODS liquid chromatography/ion trap mass spectrometry(LC/MS n) and ultra-liquid chromatography coupled with mass spectrometry(UPLC/MS) were combined in the current study for qualitative and quantitative determinations of herbacetin and its metabolites in bile,urine and feces after both oral and intravenous administration of herbacetin to rats.Enzyme kinetic studies on the intestinal and hepatic metabolism of herbacetin were further conducted to elucidate metabolic profiles of herbacetin in rat tissues and organs.Additionally,plasma concentration profiles of herbacetin and its metabolites in rats were obtained to characterize the overall pharmacokinetic behavior of herbacetin.RESULTS It was found that herbacetin was excreted primarily from rat urine in the form of glucuronide-conjugations.Subsequent in vitro enzyme kinetic studies and in vivo pharmacokinetic investigations suggested an extensive hepatic metabolism of herbacetin and the high exposure of herbacetin-glucuronides in systemic circulation.The clearance,half-life and bioavailability of herbacetin in rats were determined as(16.4±1.92)mL·kg^(-1)·min^(-1),(11.9±2.7)min,and 1.32%,respectively.On basis of these findings,a comprehensive metabolic pathway of herbacetin in rats was composed.In addition,a physiology based pharmacokinetic(PBPK) model was successfully developed with the aid of the Gastro Plus to simulate the pharmacokinetic process of herbacetin in rats.Application of the PBPK modeling can provide a useful starting point to understand and extrapolate pharmacokinetic parameters among different species,populations,and disease states.CONCLUSION After oral administration,herbacetin was subjected to colonic degradation and extensive first pass metabolism,with glucuronidation as its dominating in vivo metabol

关键词： herbacetin pharmacokinetics biotransformation glucuronidation hepatic metabolism colonic degradation