IMM Established Rhesus Macaque Model for Develop Metabolic Syndrome
Rhesus Macaque Model for Develop Metabolic Syndrome
Credit: Institute of Molecular Medicine (IMM)
As reported in the online edition of Circulation on June 20, 2012, researchers in Institute of Molecular Medicine (IMM) at Peking University have successfully established rhesus macaque model for develop metabolic syndrome. Studying in coemergence of metabolic, cardiovascular components during metabolic syndrome, and vascular dysfunction, they suggested that all of them shared underlying mechanisms. Rhesus macaques models of metabolic syndrome should be provide a valuable platform to study the pathogenesis of metabolic syndrome in relation to cardiovascular disease and diabetes mellitus.
For details, refer to the publication:Rhesus Macaques Develop Metabolic Syndrome with Reversible Vascular Dysfunction Responsive to Pioglitazone. Circulation (2012) doi: 10.1161/CIRCULATIONAHA.110.990333.
Xiuqin Zhang, Rongli Zhang, Susanne Raab, Wen Zheng, Jue Wang, Na Liu, Tiangang Zhu, Lifang Xue, Zhentao Song, Jiaming Mao, Kaitao Li, Huiliang Zhang, Yan Zhang, Chao Han, Yi Ding, Hui Wang, Ning Hou, Yuli Liu, Shujiang Shang, Chuanyun Li, Elena Sebokova, Heping Cheng and Paul L. Huang
BackgroundThe metabolic syndrome (MetS) is a constellation of clinical features that include central obesity, hypertension, atherogenic dyslipidemia, and insulin resistance. However, the concept remains controversial; it has been debated whether MetS represents nothing more than simultaneous co-occurrence of individual risk factors or whether there are common shared pathophysiological mechanisms that link the individual components.
Methods and Results
To investigate the emergence of metabolic and cardiovascular components during the development of MetS, we identified MetS-predisposed animals (n=35) in a large population of rhesus macaques (Macaca mulatta, 12.7±2.9 years old, n=408), acclimated them to standardized conditions, and monitored the progression of individual component features over 18 months. In 18 MetS animals with recently developed fasting hyperinsulinemia, central obesity, hypertension, and atherogenic dyslipidemia, we found that individual metabolic and cardiovascular components track together during the transition from pre-MetS to onset of MetS; MetS was associated with a 60% impairment of flow-mediated dilation, establishing the mechanistic link with vascular dysfunction. Pioglitazone treatment (3 mg/kg body weight/d for 6 weeks), a peroxisome proliferator-activated receptor γ agonist, reversibly improved atherogenic dyslipidemia and insulin resistance and fully restored flow-mediated dilation with persistent benefits.
Coemergence of metabolic and cardiovascular components during MetS progression and complete normalization of vascular dysfunction with peroxisome proliferator-activated receptor γ agonists suggest shared underlying mechanisms rather than separate processes, arguing for the benefit of early intervention of MetS components. Predictive nonhuman primate (NHP) models of MetS should be highly valuable in mechanistic and translational studies on the pathogenesis of MetS in relation to cardiovascular disease and diabetes mellitus.