Characterization of spontaneously-developed non-alcoholic fatty liver disease in aged rhesus monkeys

Abstract

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a global epidemic afflicting 20–30% in the general population. The animal model of NAFLD available at the present are less clinically relevant. In this study. We aimed to establish a NAFLD model of rhesus monkeys and develop an ultrasonographic steatosis score (USS) system to grade hepatic steatosis in this model.MethodsWe performed hepatic ultrasonography and blood biochemical tests on 86 rhesus monkeys with and without metabolic syndrome (MetS), among which 45 animals were further assessed by histopathological analysis.ResultsThe liver histological features of rhesus monkeys NAFLD were resemble to those of NAFLD patients. There was a close correlation between the histological steatosis grade and the USS (Spearman’s coefficient, 0.705, p < 0.001). The USS sensitivity was 87.5% and the specificity was 94.6% when the cut-off was USS2. In addition, the prevalence of MetS was significantly higher in the USS2–3 group. Multiple risk factors of cardiometabolic disease, including obesity, insulin resistance and dyslipidemia were significantly correlated with the USS.ConclusionsNAFLD was developed spontaneously among aging in rhesus monkeys (with increased prevalence in the MetS monkeys), which provided an ideal model for NAFLD. The newly developed USS system can be used to evaluate fatty liver in the rhesus monkey. The model as well as the noninvasive assessment methodology will provide a powerful tool for mechanistic studies and preclinical test of novel therapies for NAFLD.

Effects of Long-Term DHA Supplementation and Physical Exercise on Non-Alcoholic Fatty Liver Development in Obese Aged Female Mice

“…With aging, fat redistribution occurs favoring the increase in abdominal (visceral) fat and the decrease in subcutaneous fat expansion, and promoting the ectopic accumulation of fat in liver, even in non-obese, non-diabetic subjects [6,7]. Of course, the prevalence of obesity and insulin resistance, which are considered as principal risk factors for developing NAFLD increases with aging, aggravating the progression of the disease [8,9].…”

Hepatic steatosis, a lesion reported in captive aged common marmosets

“…It is characterized by an abnormal accumulation of triglycerides within the cytoplasm of hepatocytes and considered the first lesion seen in cases with non-alcoholic fatty liver disease (NAFLD) [4]. This condition is prevalent in the elderly human population and captive aged non-human primates, such as rhesus macaques (Macaca mulata) and bonnet macaques (Macaca radiata) [2,[5][6][7]. NAFLD also occurs spontaneously or is induced experimentally, by dietary changes, in other captive nonhuman primate species, such as common marmosets (Callithrix jacchus), cynomolgus macaques (Macaca fascicularis), baboons (Papio hamadryas sp.…”

“…Previous studies delineating mechanisms involved in NAFLD have largely used rodent models (for details on pathophysiological mechanisms of NAFLD/NASH see [ 11 , 12 ]). Old world non-human primates, such as rhesus macaques [ 5 ] and bonnet macaques [ 6 ] have been proposed as animal models of NAFLD/NASH in aging studies. Hepatic lesions in rhesus macaques diagnosed with NAFLD display large regions of micro- and macrovesicular steatosis [ 5 ].…”

“…Old world non-human primates, such as rhesus macaques [ 5 ] and bonnet macaques [ 6 ] have been proposed as animal models of NAFLD/NASH in aging studies. Hepatic lesions in rhesus macaques diagnosed with NAFLD display large regions of micro- and macrovesicular steatosis [ 5 ]. Although perisinusoidal and periportal fibrosis, lobular inflammation, and ballooning hepatocytes are noted in steatotic livers, these histological changes are not always observed in this model of NAFLD/NASH in aged rhesus macaques [ 5 ].…”

“…Hepatic lesions in rhesus macaques diagnosed with NAFLD display large regions of micro- and macrovesicular steatosis [ 5 ]. Although perisinusoidal and periportal fibrosis, lobular inflammation, and ballooning hepatocytes are noted in steatotic livers, these histological changes are not always observed in this model of NAFLD/NASH in aged rhesus macaques [ 5 ]. Aged rhesus macaques (older than 15-year-old) diagnosed with metabolic syndrome (defined by the presence of a cluster of metabolic factors, such as obesity, hyperglycemia, hypertriglyceridemia, hypercholesterolemia, and high blood pressure) have a higher risk of developing hepatic steatosis [ 5 ].…”