Anomalous AMPK-regulated angiotensin AT1R expression and SIRT1-mediated mitochondrial biogenesis at RVLM in hypertension programming of offspring to maternal high fructose exposure

Abstract

Background: Tissue oxidative stress, sympathetic activation and nutrient sensing signals are closely related to adult hypertension of fetal origin, although their interactions in hypertension programming remain unclear. Based on a maternal high-fructose diet (HFD) model of programmed hypertension, we tested the hypothesis that dysfunction of AMP-activated protein kinase (AMPK)-regulated angiotensin type 1 receptor (AT 1 R) expression and sirtuin1 (SIRT1)-dependent mitochondrial biogenesis contribute to tissue oxidative stress and sympathoexcitation in programmed hypertension of young offspring. Methods: Pregnant female rats were randomly assigned to receive normal diet (ND) or HFD (60% fructose) chow during pregnancy and lactation. Both ND and HFD offspring returned to ND chow after weaning, and blood pressure (BP) was monitored from age 6 to 12 weeks. At age of 8 weeks, ND and HFD offspring received oral administration of simvastatin or metformin; or brain microinfusion of losartan. BP was monitored under conscious condition by the tail-cuff method. Nutrient sensing molecules, AT 1 R, subunits of NADPH oxidase, mitochondrial biogenesis markers in rostral ventrolateral medulla (RVLM) were measured by Western blot analyses. RVLM oxidative stress was measured by fluorescent probe dihydroethidium and lipid peroxidation by malondialdehyde assay. Mitochondrial DNA copy number was determined by quantitative real-time polymerase chain reaction.

Angiotensin II receptor type 1 blocker candesartan improves morphine tolerance by reducing morphine‑induced inflammatory response and cellular activation of BV2 cells via the PPARγ/AMPK signaling pathway

“…Moreover, PPARγ can activate AMPK signaling (43,44). Notably, metformin, an AMPK activator, has been reported to reverse the increase in AT1R detected in response to a high-fructose diet (45). AT1R antagonists can regulate the proliferation and migration of vascular smooth muscle cells through AMPK/mTOR (46), and blocking AT1R can effectively inhibit activation of the AMPK/p38 MAPK/MCPIP1/ER pathway in macrophages (47).…”

Disparate Roles of Oxidative Stress in Rostral Ventrolateral Medulla in Age-Dependent Susceptibility to Hypertension Induced by Systemic l-NAME Treatment in Rats

“…The animals were placed into a stereotaxic head holder (Kopf, Tujunga, CA, USA) on a thermostatically controlled heating pad. Bilateral microinjection of the viral vectors was carried out, as described previously [ 32 , 44 ]. In brief, a glass micropipette (external tip diameter: 50–80 µm), connected to a 0.5-µL Hamilton microsyringe, was positioned into RVLM.…”

Maternal fructose intake predisposes rat offspring to metabolic disorders via abnormal hepatic programming

“…More recently, we found that maternal fructose reduces circulating high‐density lipoprotein (HDL)‐cholesterol levels in offspring, suggesting that maternal fructose consumption induces metabolic disorder in offspring. Other research groups also reported the maternal fructose intake‐induced impaired phenotypes such as hypertension, insulin resistance, and obesity 20–23 . It appears that offspring born from dams who consumed excess fructose are prone to physiological dysfunctions.…”

“…Other research groups also reported the maternal fructose intake-induced impaired phenotypes such as hypertension, insulin resistance, and obesity. [20][21][22][23] It appears that offspring born from dams who consumed excess fructose are prone to physiological dysfunctions. However, previous studies have focused primarily on phenotypic analysis.…”