Abstract
Non‐alcoholic fatty liver disease (NAFLD) is a growing concern globally, and is associated with obesity, hyperlipemia, hypertension, insulin resistance, and diabetes; all traits linked to metabolic syndrome, which affects 20% of the US population. While angiotensin receptor blockers (ARB) effectively ameliorate the hypertension associated with metabolic disorders, its potential benefits on other aspects of metabolism during such conditions are not fully appreciated. ARB treatment may reduce overproduction and accumulation of hepatic triacylglycerols (TG), but it remains unknown whether ARB treatment has favorable effects in fatty livers associated with insulin resistance. To evaluate the benefits of the ARB treatment on lipid‐related genes, three groups (n=4–6) of 25‐week‐old rats were used: (1) LETO (lean strain‐control), (2) insulin resistant OLETF, and 3) OLETF + ARB (10 mg olmesartan/kg/d × 8 wks). An oral glucose tolerance test (oGTT) was performed to mimic a high glucose challenge. Liver and plasma were collected at T0, T30, and T60 min of the oGTT. We measured gene expression of hepatic PPARα, SREBP1c, FASN, and CPT1 along with TG and cholesterol levels in liver and plasma. PPARα expression was 1.6‐fold lower at T0 in OLETF+ARB compared with OLETF, but no changes were detected for other genes evaluated. Hepatic TG content was 1.5‐, 3.4‐ and 1.5‐fold lower at T0, T30, and T60, respectively, in OLETF+ARB compared to OLETF, along with 1.2‐fold lower plasma TG at T30. These changes suggest that AT1 signaling contributes to stabilizing lipid metabolism especially during a glucose challenge, and contributes to maintaining lower hepatic TG content that translates to reduced plasma TG during a glucose challenge.Support or Funding InformationM. Thorwald was supported by NIH NCMHD9T37MD001480. R.M. Ortiz was partially supported by NIH NHLBIK02HL103787. Research was partially funded by NIH NHLBIR01HL091767.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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