DOI: 10.1002/ame2.70124
Chronic high-fat diet induces multi-organ dysfunction and metabolic homeostasis disruption in Macaca fascicularis
Hongyi Chen1
Wei Liu2
Dan Zhou3
Shuhua Liu1
Yalun Guan1
Zongyu Miao1
Lei Cai1
Xuejiao Li1
Yunfeng Li1
Zhongqiang Huang1
Yi Jin4
Ge Li5
Yu Zhang1
1.Guangdong Provincial Biotechnology Research Institute(Guangdong Provincial Laboratory Animals Monitoring Center),Guangzhou,China2.Guangzhou Huazhen Biosciences Co.,Ltd.,Guangzhou,China3.Department of Geriatrics,Shenzhen People's Hospital(The Second Clinical Medical College,Jinan University,The First Affiliated Hospital,Southern University of Science and Technology;Shenzhen Clinical Research Center for Geriatrics;Guangdong Provincial Clinical Research Center for Geriatrics),Shenzhen,China4.Shenzhen Institute for Drug Control(Shenzhen Testing Center of Medical Devices),Shenzhen,China5.Guangdong Provincial Biotechnology Research Institute(Guangdong Provincial Laboratory Animals Monitoring Center),Guangzhou,China;Guangzhou National Laboratory,Guangzhou,China
摘要：Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.
Methods:Thirty-five male macaques aged 10-15years underwent an 18-month HFD intervention.Physiological parameters(BMI,BP,hematology),liver fat fraction(evaluated by ultrasound/MRI),cardiac function(assessed by echocardiography),and histopathology(using liver biopsy)were measured before and after the intervention.Serum proteomics with KEGG/STRING analyses identified molecular mechanisms.
Results:Within 6months,HFD induced dyslipidemia(elevated TG,TCHO,HDL-C,LDL-C).After 18 months,metabolic dysfunction-associated steatohepatitis(MASH)was confirmed by histopathology in 57.14％(16/28)of macaques,diabetes(elevated FPG/HbA1c)in 17.86％(5/28),and myocardial hypertrophy(elevated LVMass/LAD)in 46.43％(13/28).Proteomics identified Bile acid-CoA:amino acid N-acyltransferase(BAAT)as a MASH hallmark protein,the level of which was inversely correlated with the degree of fibrosis.For diabetes,citrate synthase(CS)and malate dehydrogenase 1(MDH1)impaired glucose oxidation via the TCA cycle,while hexose-6-phosphate de-hydrogenase(H6PD)disrupted gluconeogenesis.Myocardial hypertrophy was associ-ated with the downregulation of SRC proto-oncogene,non-receptor tyrosine kinase(SRC),mitogen-activated protein kinase 14(MAPK14),emerin(EMD),and integrin subunit beta 1(ITGB1).
Conclusions:An 18-month HFD successfully established a translational M.fascicula-ris model replicating key metabolic disorders(MASH,diabetes,cardiac hypertrophy).BAAT,CS/MDH1/H6PD,and SRC/MAPK14/EMD/ITGB1 were identified as mecha-nistic biomarkers for these conditions.
机标关键词：metabolicchronicdietdisruptiondysfunctionfascicularishigh-fathomeostasis
论文发表日期：2026-01-30
在线出版日期：2026-03-27（本平台首次上网日期，不代表文献的发表时间）
页数：14( 193-206 )
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