Adipose Angiotensinogen is Upregulated during Insulin Resistance in OLETF Rats

Abstract

Activation of the renin‐angiotensin system (RAS) has been shown to contribute to metabolic syndrome. Hyptertension is a key component of metabolic syndrome and is regulated by RAS. The Otsuka Long‐Evans Tokushima Fatty (OLETF) rat is a relatively new and highly relevant model because its pathogenesis of insulin resistance, metabolic syndrome, and type 2 diabetes closely resembles that of the progression of the human condition. However, the contribution of adipose RAS to metabolic syndrome is not well defined. To address the hypothesis that adipose RAS activation is increased with insulin resistance, rats were divided into two groups (n=10–12/group): 1) lean strain‐control LETO and 2) obese insulin resistant OLETF. Systolic blood pressure (SBP) was measured weekly for 24 weeks and insulin resistance index (IRI) was determined at 9 and 24 weeks. Tissue samples were collected from each group (n=5–6/group) at 15 and 24 weeks. Mean SBP from OLETF was 28% and 27% greater compared to that of the LETO after 15 and 24 wk respectively. Mean IRI was greater at both time periods and was exacerbated in 24 wk OLETF compared to 15 wk. By 24 wk, adipose angiotensinogen (angiotensin precursor) expression had increased in 24 wk OLETF suggesting that activation of adipose RAS was increased. The data suggest that increased activation of adipose RAS may contribute to the increased metabolic disorders (SBP and IRI) commonly associated with metabolic syndrome.