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High-fat diet induces cardiac remodelling and dysfunction: assessment of the role played by SIRT3 loss.

Zeng H, Vaka VR, He X, Booz GW, Chen JX - J. Cell. Mol. Med. (2015)

Bottom Line: HFD resulted in a significant reduction in SIRT3 expression in the heart.SIRT3 KO mice fed HFD showed greater ROS production and a further reduction in cardiac function compared to SIRT3 KO mice on ND.However, HFD did not further reduce capillary density in SIRT3 KO hearts, implicating SIRT3 loss in HFD-induced capillary rarefaction.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, The University of Mississippi Medical Center, School of Medicine, Jackson, MS, USA.

No MeSH data available.


Related in: MedlinePlus

HIF-1α and HIF-2α are reduced by HFD and SIRT3 loss in the heart. WT and SIRT3 KO mice were fed ND or HFD for 16 weeks. Hearts were extracted and Western blot analysis was performed on ventricular lysates. (A) Representative blot of HIF-1α. Blot was stripped and reprobed for GAPDH as a loading control. Bar graph shows mean ± SEM for n = 6. PI = ns, PD and PS ≤ 0.01; *P ≤ 0.05; **P ≤ 0.01. (B) Representative blots of HIF-2α and GAPDH. Values are mean ± SEM (n = 6 ND and 5–7 HFD). PI = ns, PD ≤ 0.05, PS ≤ 0.01; *P ≤ 0.05; **P ≤ 0.01.
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fig06: HIF-1α and HIF-2α are reduced by HFD and SIRT3 loss in the heart. WT and SIRT3 KO mice were fed ND or HFD for 16 weeks. Hearts were extracted and Western blot analysis was performed on ventricular lysates. (A) Representative blot of HIF-1α. Blot was stripped and reprobed for GAPDH as a loading control. Bar graph shows mean ± SEM for n = 6. PI = ns, PD and PS ≤ 0.01; *P ≤ 0.05; **P ≤ 0.01. (B) Representative blots of HIF-2α and GAPDH. Values are mean ± SEM (n = 6 ND and 5–7 HFD). PI = ns, PD ≤ 0.05, PS ≤ 0.01; *P ≤ 0.05; **P ≤ 0.01.

Mentions: We previously reported that impaired HIF signalling is associated with reduced myocardial capillary density in obese diabetic mouse model 11. Hence, we examined HIF levels in diet-induced obesity model. As seen from Fig.6A and B, cardiac HIF-1α and HIF-2α levels were reduced in mice fed HFD compared to mice fed ND for 16 weeks. Hypoxia-inducible factor-1α and -2α levels were also significantly reduced in hearts of SIRT3 KO mice compared to WT mice (Fig.6A and B). Hypoxia-inducible factor-1α levels were further decreased in SIRT3 KO-DIO mice compared to SIRT3 KO mice (Fig.6A and B). Levels of HIF-2α tended to be further reduced by HFD in SIRT3 KO hearts, but this did not reach significance. No interaction between HFD and SIRT3 loss on HIF-1α and -2α levels was demonstrated.


High-fat diet induces cardiac remodelling and dysfunction: assessment of the role played by SIRT3 loss.

Zeng H, Vaka VR, He X, Booz GW, Chen JX - J. Cell. Mol. Med. (2015)

HIF-1α and HIF-2α are reduced by HFD and SIRT3 loss in the heart. WT and SIRT3 KO mice were fed ND or HFD for 16 weeks. Hearts were extracted and Western blot analysis was performed on ventricular lysates. (A) Representative blot of HIF-1α. Blot was stripped and reprobed for GAPDH as a loading control. Bar graph shows mean ± SEM for n = 6. PI = ns, PD and PS ≤ 0.01; *P ≤ 0.05; **P ≤ 0.01. (B) Representative blots of HIF-2α and GAPDH. Values are mean ± SEM (n = 6 ND and 5–7 HFD). PI = ns, PD ≤ 0.05, PS ≤ 0.01; *P ≤ 0.05; **P ≤ 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4549035&req=5

fig06: HIF-1α and HIF-2α are reduced by HFD and SIRT3 loss in the heart. WT and SIRT3 KO mice were fed ND or HFD for 16 weeks. Hearts were extracted and Western blot analysis was performed on ventricular lysates. (A) Representative blot of HIF-1α. Blot was stripped and reprobed for GAPDH as a loading control. Bar graph shows mean ± SEM for n = 6. PI = ns, PD and PS ≤ 0.01; *P ≤ 0.05; **P ≤ 0.01. (B) Representative blots of HIF-2α and GAPDH. Values are mean ± SEM (n = 6 ND and 5–7 HFD). PI = ns, PD ≤ 0.05, PS ≤ 0.01; *P ≤ 0.05; **P ≤ 0.01.
Mentions: We previously reported that impaired HIF signalling is associated with reduced myocardial capillary density in obese diabetic mouse model 11. Hence, we examined HIF levels in diet-induced obesity model. As seen from Fig.6A and B, cardiac HIF-1α and HIF-2α levels were reduced in mice fed HFD compared to mice fed ND for 16 weeks. Hypoxia-inducible factor-1α and -2α levels were also significantly reduced in hearts of SIRT3 KO mice compared to WT mice (Fig.6A and B). Hypoxia-inducible factor-1α levels were further decreased in SIRT3 KO-DIO mice compared to SIRT3 KO mice (Fig.6A and B). Levels of HIF-2α tended to be further reduced by HFD in SIRT3 KO hearts, but this did not reach significance. No interaction between HFD and SIRT3 loss on HIF-1α and -2α levels was demonstrated.

Bottom Line: HFD resulted in a significant reduction in SIRT3 expression in the heart.SIRT3 KO mice fed HFD showed greater ROS production and a further reduction in cardiac function compared to SIRT3 KO mice on ND.However, HFD did not further reduce capillary density in SIRT3 KO hearts, implicating SIRT3 loss in HFD-induced capillary rarefaction.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, The University of Mississippi Medical Center, School of Medicine, Jackson, MS, USA.

No MeSH data available.


Related in: MedlinePlus