biostudies-literatureChen HTechnology Planning Project of LinzhiNational Key Research and Development Program of ChinaScience and Technology Projects in GuangzhouGuangdong S&T programme193-206https://www.ebi.ac.uk/biostudies/studies/S-EPMC12907977biostudies-literatureUnknown9(1)<h4>Background</h4>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.<h4>Methods</h4>Thirty-five male macaques aged 10-15 years 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.<h4>Results</h4>Within 6 months, 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 dehydrogenase (H6PD) disrupted gluconeogenesis. Myocardial hypertrophy was associated 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).<h4>Conclusions</h4>An 18-month HFD successfully established a translational M. fascicularis model replicating key metabolic disorders (MASH, diabetes, cardiac hypertrophy). BAAT, CS/MDH1/H6PD, and SRC/MAPK14/EMD/ITGB1 were identified as mechanistic biomarkers for these conditions.Animal models and experimental medicineChronic high-fat diet induces multi-organ dysfunction and metabolic homeostasis disruption in Macaca fascicularis.PMC129079772022060101972021YFF07022002023-YZ-012022060100842022060600022023B03030400042009A081000002Li GCai LChen HLiu SJin YLiu WLi XGuan YLi YHuang ZZhang YZhou DMiao ZfalseChronic high-fat diet induces multi-organ dysfunction and metabolic homeostasis disruption in Macaca fascicularis.<h4>Background</h4>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.<h4>Methods</h4>Thirty-five male macaques aged 10-15 years 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.<h4>Results</h4>Within 6 months, 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 dehydrogenase (H6PD) disrupted gluconeogenesis. Myocardial hypertrophy was associated 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).<h4>Conclusions</h4>An 18-month HFD successfully established a translational M. fascicularis model replicating key metabolic disorders (MASH, diabetes, cardiac hypertrophy). BAAT, CS/MDH1/H6PD, and SRC/MAPK14/EMD/ITGB1 were identified as mechanistic biomarkers for these conditions.2026-01-01T00:00:00Z2026 Jan2026-07-15T16:24:47.324Z2026-07-07T03:08:21.494ZS-EPMC129079774153130610.1002/ame2.70124