Key result
Global Sirt1 overexpression prevented the increase in pulse wave velocity observed in wild-type mice after 12 weeks of a Western diet (p<0.04 for WT increase).
Why the study?
Increased arterial stiffness is a cardiovascular risk factor in Western diet-induced obesity, and activation of Sirt1 has been associated with vasoprotection in aged mice, but the effect of Sirt1 overexpression on diet-induced arterial stiffening was unclear.
Does Sirt1 overexpression prevent Western diet-induced arterial stiffening in mice?
Does Sirt1 overexpression prevent Western diet-induced arterial stiffening in mice?
Global Sirt1 overexpression in mice limits the increase in arterial stiffness and glucose intolerance induced by a Western diet.
Answers are grounded in this paper and cite their sources.
Sirt1 overexpression may limit diet-induced arterial stiffening in mice; leaves open translation to human cardiometabolic disease.
Increased arterial stiffness is a cardiovascular disease risk factor in the setting of advancing age and Western diet (WD) induced obesity. Increases in large artery stiffness, as measured by pulse wave velocity (PWV), occur within 8 weeks of WD feeding in mice. Sirtuin‐1 (Sirt1), a NAD‐dependent deacetylase, regulates cellular metabolic activity and activation of this protein has been associated with vasoprotection in aged mice. The aim of the study was to elucidate the effect of global Sirt1 overexpression (Sirt tg ) on WD‐induced arterial stiffening. Sirt1 overexpression did not influence PWV in normal chow (NC) fed mice. However, PWV was higher in wild‐type (WT) mice ( p < 0.04), but not in Sirt tg mice, after 12 weeks of WD and this effect was independent of changes in blood pressure or the passive pressure diameter relation in the carotid artery. Overexpression of Sirt1 was associated with lower collagen and higher elastin mRNA expression in the aorta of WD fed mice (both p < 0.05). Although MMP2 and MMP3 mRNA were both upregulated in WT mice after WD (both p < 0.05), this effect was reversed in Sirt tg mice compared to WT mice fed WD (both p < 0.05). Surprisingly, histologically assessed collagen and elastin quality were unchanged in the aortas of WT or Sirt tg mice after WD. However, Sirt tg mice were protected from WD‐induced glucose intolerance, although there was no difference in insulin tolerance between groups. These findings demonstrate a vasoprotective effect of Sirt1 overexpression that limits the increase in arterial stiffness in response to consumption of a WD.
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Gogulamudi et al. (2022) studied Western diet-induced aortic stiffening. Global Sirt1 overexpression vs. Wild-type mice was evaluated on Pulse wave velocity (PWV) (p=<0.04). Global Sirt1 overexpression prevented the increase in pulse wave velocity observed in wild-type mice after 12 weeks of a Western diet (p<0.04 for WT increase).
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