Antihypertensive therapy improves insulin resistance and serum levels of interleukin-6 and -10 in spontaneously hypertensive rats with steatohepatitis

Kozono,Masaya; Uto,Hirofumi; Ibusuki,Rie; Arima,Shiho; Oda,Kohei; Taguchi,Hiroki; Sasaki,Fumisato; Nasu,Yuichiro; Hashimoto,Shinichi; Setoyama,Hitoshi; Kanmura,Shuji; Numata,Masatsugu; Tsubouchi,Hirohito; Ido,Akio

doi:10.3892/mmr.2016.5875

Antihypertensive therapy improves insulin resistance and serum levels of interleukin-6 and -10 in spontaneously hypertensive rats with steatohepatitis

Authors:
- Masaya Kozono
- Hirofumi Uto
- Rie Ibusuki
- Shiho Arima
- Kohei Oda
- Hiroki Taguchi
- Fumisato Sasaki
- Yuichiro Nasu
- Shinichi Hashimoto
- Hitoshi Setoyama
- Shuji Kanmura
- Masatsugu Numata
- Hirohito Tsubouchi
- Akio Ido
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Affiliations: Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890‑8544, Japan, Department of HGF Tissue Repair and Regenerative Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890‑8544, Japan
Published online on: October 21, 2016 https://doi.org/10.3892/mmr.2016.5875
Pages: 5385-5394

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Abstract

Metabolic syndrome based on insulin resistance (IR) and hypertension is a risk factor for advanced liver disease and cardiovascular disease in patients with nonalcoholic steatohepatitis (NASH). The present study investigated the effects of severe hypertension induced by a high‑salt (HS) diet and antihypertensive therapy on the pathophysiological condition of spontaneously hypertensive rats (SHRs) with steatohepatitis. Steatohepatitis was induced using a choline-deficient, L-amino acid-defined diet (CDAA). Male SHRs (7‑week‑old) were randomly divided into five groups: Those receiving 6 weeks of standard chow with a normal salt concentration, followed by an additional 8 weeks of standard chow or CDAA with a normal salt concentration (control and CDAA groups, respectively); and those receiving 6 weeks of standard chow with HS, followed by CDAA with HS for an additional 8 weeks, with or without the antihypertensive agents, amlodipine (Aml) or hydralazine. In the CDAA and CDAA+HS groups, blood pressure was significantly correlated with serum levels of insulin, fasting blood glucose and homeostasis model assessment (HOMA)‑IR. Antihypertensive therapy ameliorated the elevated glucose, insulin and HOMA‑IR. Furthermore, the increased levels of serum interleukin (IL)‑6 following the CDAA+HS diet were attenuated by antihypertensive therapy. The serum levels of IL‑10 were increased by antihypertensive therapy, and the decrease in the proportion of splenic CD4+CD25+forkhead box P3+ T cells observed following the CDAA+HS diet tended to be restored by Aml. In conclusion, antihypertensive therapy improved glucose metabolism and imbalances in cytokine expression in the rat model of hypertension with steatohepatitis, suggesting that antihypertensive therapy acting through immunological factors may be beneficial for patients with metabolic syndrome-associated NASH.

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