‘Memory’ and ‘legacy’ in hypertension and lifestyle-related diseases

Sasamura, Hiroyuki; Itoh, Hiroshi

doi:10.1038/hr.2011.222

Cited by 4 publications

(3 citation statements)

References 10 publications

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“…We have included previously published [ 36 ] body mass and plasma angiotensin II levels (Table 1 ) to better illustrate our model and the efficacy of the ARB treatment. Additionally, we examine the potential detriments of non-compliance with ARB treatment after the initial treatment has stopped (legacy effect) [ 39 ]. Low compliance has proven to be a challenge when treating patients with hypertension, dyslipidemia, and diabetes [ 40 , 41 ] and assessing ARB-legacy effects may provide a better understanding of the detriments to removal of treatment [ 42 , 43 ].…”

Section: Methodsmentioning

confidence: 99%

Chronic angiotensin receptor activation promotes hepatic triacylglycerol accumulation during an acute glucose challenge in obese-insulin-resistant OLETF rats

et al. 2021

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Purpose Angiotensin receptor blockers (ARBs) can ameliorate metabolic syndrome (MetS)-associated dyslipidemia, hepatic steatosis, and glucose intolerance, suggesting that angiotensin receptor (AT1) over-activation contributes to impaired lipid and glucose metabolism, which is characteristic of MetS. The aim of this study was to evaluate changes in the lipid profile and proteins of fatty acid uptake, triacylglycerol (TAG) synthesis, and β-oxidation to better understand the links between AT1 overactivation and non-alcoholic fatty liver disease (NAFLD) during MetS. Methods Four groups of 25-week-old-rats were used: (1) untreated LETO, (2) untreated OLETF, (3) OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan/kg/d × 8 weeks) and (4) OLETF ± ARB (MINUS; 10 mg olmesartan/kg/d × 4 weeks, then removed until dissection). To investigate the dynamic shifts in metabolism, animals were dissected after an oral glucose challenge (fasting, 3 and 6 h post-glucose). Results Compared to OLETF, plasma total cholesterol and TAG remained unchanged in ARB. However, liver TAG was 55% lesser in ARB than OLETF, and remained lower throughout the challenge. Basal CD36 and ApoB were 28% and 29% lesser, respectively, in ARB than OLETF. PRDX6 abundance in ARB was 45% lesser than OLETF, and it negatively correlated with liver TAG in ARB. Conclusions Chronic blockade of AT1 protects the liver from TAG accumulation during glucose overload. This may be achieved by modulating NEFA uptake and increasing TAG export via ApoB. Our study highlights the contributions of AT1 signaling to impaired hepatic substrate metabolism and the detriments of a high-glucose load and its potential contribution to steatosis during MetS.

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Section: Methodsmentioning

confidence: 99%

Chronic angiotensin receptor activation promotes hepatic triacylglycerol accumulation during an acute glucose challenge in obese-insulin-resistant OLETF rats

et al. 2021

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“…LETO and OLETF rats were assigned to the following groups (n = 6-8 animals/group/ time point): 1) untreated LETO, 2) untreated OLETF, and 3) OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan/kg/d × 8 wk), and 4) OLETF ± ARB (10 mg olmesartan/kg/d × 4 wks then removed until dissection). The ARB removal group allowed us to assess the impacts of compliance and potential legacy effects [17,18] with respect to AT1 signaling, which has not be studied under T2DM conditions. ARB (Daiichi-Sankyo, Tokyo, Japan) was administered by oral gavage suspended in carboxymethyl cellulose (CMC) to conscious rats [15].…”

Section: Animalsmentioning

confidence: 99%

“…While chronic ARB treatment during a glucose challenge in insulin resistant conditions increased Nrf2 nuclear binding and improved cardiac mitochondrial function [15,16], the possible benefits of chronic ARB treatment on Nrf2 signaling and mitochondrial function during a glucose challenge in T2DM hearts has not been explored. Additionally, the significance of compliance and the "cell memory" or "legacy effect" with respect to AT1 signaling during T2DM has not been examined [17,18]. We hypothesized that an acute elevation in glucose impairs Nrf2-related gene expression in diabetic hearts, while AT1 antagonism would aid in Nrf2mediated antioxidant production and energy replenishment.…”

Section: Introductionmentioning

confidence: 99%