Ketogenic diet aggravates cardiac remodeling in adult spontaneously hypertensive rats

Fig. 1. Ketogenic diet contributed to hypertension and cardiac remodeling in spontaneously hypertensive rats. a Ketogenic diet (KD) increased the intramyocardial β-hydroxybutyrate content. b systolic blood pressure (SBP), diastolic blood pressure (DBP). c heart rate. d and body weight. e were measured. f KD feeding increased ration of heart weight-to-body weight of spontaneously hypertensive rats. g Cardiomyocyte cross-sectional area in left ventricular tissue was measured by WGA. Scale bar, 50 μm. The statistical results were shown in H. Values are the mean ± SEM. n = 4 for each ND group. n = 8 for each KD group. *P < 0.05, **P < 0.01

Fig. 2. Ketogenic diet aggravated interstitial fibrosis in the heart of spontaneously hypertensive rats. a Ketogenic diet increased the expression of collagen in the heart of spontaneously hypertensive rats. The statistical results are shown in b and c. d Masson trichrome stain was used on the left ventricular tissue to visualize interstitial fibrosis in hearts. Scale bar, 100 μm. The statistical results are shown in E. Values are the mean ± SEM. n = 4 for each group. *P < 0.05, **P < 0.01

Fig. 3. Ketogenic diet promoted oxidative stress injury in spontaneously hypertensive rats. a The expression of SOD2 and NOX4 in the heart was measured by western blotting. The quantified SOD2 and NOX4 results are shown in b and c. d ketogenic diet decreased the SOD activity and increased the malondialdehyde (MDA) contents e in the heart of SHRs. f ketogenic diet decreased the GSH contents in the heart of SHRs. Values are the mean ± SEM. n = 4 for each group. *P < 0.05, **P < 0.01

Fig. 4. Ketogenic diet enhanced inflammatory responses in the heart of spontaneously hypertensive rats. a Ketogenic diet increased the expression of MCP-1 and TNFα in the heart of SHRs. The quantified MCP-1 and TNFα results are shown in b and c. d–e Heart sections were stained with myeloperoxidase to evaluate eosinophilic infiltration. f–g Heart sections were Immunohistochemical staining of CD68 to evaluate macrophage accumulation. Values are the mean ± SEM. n = 4 for each group. *P < 0.05, **P < 0.01

Fig. 5. Ketogenic diet activated mTORC2 in the heart of spontaneously hypertensive rats. a The phosphorylation of AMPK and the ratio of p-S6/S6 and p-Akt/Akt in the heart of Wistar rats and SHRs were measured with Western blots. The quantitative result were shown in b–d. Values are the mean ± SEM. n = 4 for each group. *P < 0.05, **P < 0.01

Fig. 6. β-hydroxybutyrate strengthened the progression of TGF-β-induced fibrosis via mTOR pathway in isolated cardiac fibroblasts. a Cardiac fibroblasts were incubated with β-hydroxybutyrate (β-OHB) and TGF-β. Then the activation of mTOR and the expression of collagen were measured. The quantified results are shown in b–e. f–h The effects of co-stimuli of β-OHB and TGF-β in cardiac fibroblasts were blunted by the mTOR inhibitor Temsirolimus. i inhibition of mTOR with Temsirolimus suppressed β-OHB and TGF-β-induced proliferation in cardiac fibroblasts. Values are the mean ± SEM. n = 4–6 for each group. *P < 0.05, **P < 0.01