Yong - Fu Xiao
University of Rutgers, USA
Title: Cardiac, hepatic and renal complications in spontaneously developed diabetic nonhuman primates
Biography
Biography: Yong - Fu Xiao
Abstract
Obesity can lead to insulin resistant and Type 2 diabetes mellitus (T2DM). Both obesity and diabetes are serious epidemic issues in developed and some developing countries. T2DM and obesity often complicate each other and escalate patients’ other healthiness. Cardiac, hepatic and renal complications of diabetes and obesity have widely been reported and studied for decades. However, the underlying mechanisms and interactions between obesity and diabetes have yet to be elucidated further. Nonhuman primates (NHPs) can spontaneously develop obesity and diabetes which are the highly valuable models for research to delineate molecular and cellular mechanisms of their pathophysiology. In our housed dysglycemic and dyslipidemic cynomolgus monkeys we evaluated cardiac, hepatic and renal complications. Echocardiography in diabetic NHPs showed left ventricular systolic and diastolic dysfunctions accompanied with left atrial hypertrophic remodeling, the phenotypes similarly to those found in diabetic patients. In addition, dyslipidemic and diabetic monkeys can develop nonalcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH) assembling to the human liver disease. We also evaluated diabetic nephropathy and its molecular mechanisms in diabetic NHPs with significantly high albuminuria. Transcriptome analysis of kidney biopsies showed differentially expressed genes (DEGs) with 75DEGs related to diabetic nephropathy, but only 1 nephropathy specific gene (LCT lactase) and 4 other DEGs were highly altered in diabetic monkeys with albuminuria. Signaling pathway analysis of the relevant DEGs and encoded proteins highlighted the role of a kidney failure, renal and urological diseases, and inflammatory diseases related network, in which the most pivotal gene in this network is Tumor Necrosis Factor, indicating that nephropathy is a disease closely related to inflammation and cell death. Therefore, noninvasive echocardiography and quantitative biomarker measurements in NHP models can be powerful translational tools for evaluation of obesity and diabetes complications and for investigation of potential novel therapies due to the pathophysiological similarity between NHP and humans.