Background
Hypertension may result in atrial fibrillation (AF) and lipid metabolism disorders. The Sirtuins3 (SIRT3) / AMP-activated protein kinase (AMPK) signaling pathway has the capacity to regulate lipid metabolism disorders and the onset of AF. We hypothesize that the SIRT3/AMPK signaling pathway suppresses lipid metabolism disorders, thereby mitigating salt-sensitive hypertension (SSHT)-induced susceptibility to AF.
Conclusions
We have confirmed that high-salt diet can result in hypertension, associated atrial tissue lipid metabolism dysfunction. This condition is linked to the inhibition of the SIRT3/AMPK signaling pathway, which plays a significant role in the progression of susceptibility to AF in SSHT rats.
Methods
The study involved 7-week-old male Dahl salt-sensitive that were fed either high-salt diet (8% NaCl; DSH group) or normal diet (0.3% NaCl; DSN group). Then DSH group were administered either oral metformin (MET, an AMPK agonist) or intraperitoneal injection of Honokiol (HK, a SIRT3 agonist). This experimental model allowed for the measurement of SBP, the expression levels of lipid metabolism-related biomarker, pathological examination of atrial fibrosis and lipid accumulation, as well as AF inducibility and AF duration.
Results
DSH decrease SIRT3, phosphorylation-AMPK and VLCAD expression, increased FASN and FABP4 expression and concentrations of FFA and TG, atrial fibrosis and lipid accumulation in atrial tissue, enhanced level of SBP, promoted AF induction rate and prolonged AF duration, which are blocked by MET and HK. Our results also showed that the degree of atrial fibrosis was negatively correlated with VLCAD expression, but positively correlated with the expression of FASN and FABP4. Conclusions: We have confirmed that high-salt diet can result in hypertension, associated atrial tissue lipid metabolism dysfunction. This condition is linked to the inhibition of the SIRT3/AMPK signaling pathway, which plays a significant role in the progression of susceptibility to AF in SSHT rats.