Lipid profile and liver lipids of OLETF rats during ARB treatment and after its removal

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The metabolic syndrome (MetS) affects 20% of the US population. MetS comprises several disorders that raise the risk of atherosclerosis, insulin resistance, and diabetes. Angiotensin receptor blockers (ARBs) are used to ameliorate hypertension associated with metabolic disorders. Nonetheless, the potential benefits of ARBs on the metabolic state are not fully appreciated. ARB treatment reduces overproduction and accumulation of hepatic triacylglycerols (TAG), but whether ARB treatment has favorable effects in fatty livers associated with insulin resistance is still unknown. Furthermore, the compliance on the usage of ARBs should also be addressed, as MetS patients may be under variating treatments, exposing them to secondary effects due to the ARB treatment removal. To evaluate the benefits of ARB treatment and implications of its removal on the lipid profile, four groups (n=4–6) of 25‐week‐old rats were used: (1) lean, strain‐control Long‐Evans Tokoshima Otsuka (LETO), (2) obese, insulin resistant Otsuka Long‐Evans Tokoshima Fatty (OLETF), 3) ARB‐treated OLETF, (10 mg olmesartan/kg/d × 8 wks), and 4) OLETF ± ARB (10 mg olmesartan/kg/d × 4 wks then removed until dissection). An oral glucose challenge (GC) was performed prior to dissection and tissues collected from a subset of animals in each group at defined time points (T0, 3 an 6hr). We measured different components of the lipid profile, during the ARB treatment and after its removal. Plasma NEFA, TAG and cholesterol levels remain unchanged with ARB treatment, as well as with ARB removal. ARB treatment did not change the liver levels of cholesterol, but prevented the increase shown by OLETFs during the GC. ARB removal shown increased cholesterol after 6 hr of the GC. ARB treatment decreased liver TAG and throughout the GC. ARB removal increased TAG liver levels during the GC. Suggesting that lipid profiles may not change during static sampling during or after ARB treatment. ARB treatment reduces liver TAG concentration, and even with ARB removal suggesting that plasma levels do not accurately reflect tissue levels. Following the GC, the ARB removal group demonstrated an increase in levels, suggesting that treatment non‐compliance results in rapid return to basal levels and increased potential for hepatic dysfunction. Further investigation on lipid transport and metabolic regulation during ARB treatment and removal may yield insight for a wider perspective for treatment of traits linked to MetS.Support or Funding InformationThis work was supported by NIH MHIRT.