β-Catenin Regulates Cardiac Energy Metabolism in Sedentary and Trained Mice

Balatskyi, V. V.; Palchevska, Oksana; Bortnichuk, Lina; Gan, Ana-Maria; Myronova, Anna; Macewicz, L. L.; Navrulin, Viktor O.; Tumanovska, Lesya V.; Olichwier, Adam; Dobrzyń, Paweł; Piven, O. O.

doi:10.3390/life10120357

Cited by 9 publications

(26 citation statements)

References 57 publications

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“…25,26 After birth, βcatenin promotes the hypertrophic growth of cardiomyocytes. 27,28 Its signaling activity decreases during heart maturation and remains low in the healthy adult heart, but it is still essential for maintaining heart function. [28][29][30] The reactivation of WNT/β-catenin pathway occurs in response to pathological stimuli.…”

Section: Introductionmentioning

confidence: 99%

WNT/β‐catenin pathway is a key regulator of cardiac function and energetic metabolism

et al. 2023

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The WNT/β‐catenin pathway is a master regulator of cardiac development and growth, and its activity is low in healthy adult hearts. However, even this low activity is essential for maintaining normal heart function. Acute activation of the WNT/β‐catenin signaling cascade is considered to be cardioprotective after infarction through the upregulation of prosurvival genes and reprogramming of metabolism. Chronically high WNT/β‐catenin pathway activity causes profibrotic and hypertrophic effects in the adult heart. New data suggest more complex functions of β‐catenin in metabolic maturation of the perinatal heart, establishing an adult pattern of glucose and fatty acid utilization. Additionally, low basal activity of the WNT/β‐catenin cascade maintains oxidative metabolism in the adult heart, and this pathway is reactivated by physiological or pathological stimuli to meet the higher energy needs of the heart. This review summarizes the current state of knowledge of the organization of canonical WNT signaling and its function in cardiogenesis, heart maturation, adult heart function, and remodeling. We also discuss the role of the WNT/β‐catenin pathway in cardiac glucose, lipid metabolism, and mitochondrial physiology.

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Section: Introductionmentioning

confidence: 99%

WNT/β‐catenin pathway is a key regulator of cardiac function and energetic metabolism

et al. 2023

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“…β-catenin was able to transfer into the nucleus to affect the expression of hypertrophy-related genes [ 46 ]. When β-catenin haplo-insufficient mice were subjected to endurance training, the cardiomyocytes’ hypertrophic growth was attenuated [ 47 ]. This suggests that inhibition of β-catenin could decrease cardiac hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Notch1 Is Involved in Physiologic Cardiac Hypertrophy of Mice via the p38 Signaling Pathway after Voluntary Running

Zhang

Liu

et al. 2023

IJMS

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Appropriate exercise such as voluntary wheel-running can induce physiological cardiac hypertrophy. Notch1 plays an important role in cardiac hypertrophy; however, the experimental results are inconsistent. In this experiment, we aimed to explore the role of Notch1 in physiological cardiac hypertrophy. Twenty-nine adult male mice were randomly divided into a Notch1 heterozygous deficient control (Notch1+/− CON) group, a Notch1 heterozygous deficient running (Notch1+/− RUN) group, a wild type control (WT CON) group, and a wild type running (WT RUN) group. Mice in the Notch1+/− RUN and WT RUN groups had access to voluntary wheel-running for two weeks. Next, the cardiac function of all of the mice was examined by echocardiography. The H&E staining, Masson trichrome staining, and a Western blot assay were carried out to analyze cardiac hypertrophy, cardiac fibrosis, and the expression of proteins relating to cardiac hypertrophy. After two-weeks of running, the Notch1 receptor expression was decreased in the hearts of the WT RUN group. The degree of cardiac hypertrophy in the Notch1+/− RUN mice was lower than that of their littermate control. Compared to the Notch1+/− CON group, Notch1 heterozygous deficiency could lead to a decrease in Beclin-1 expression and the ratio of LC3II/LC3I in the Notch1+/− RUN group. The results suggest that Notch1 heterozygous deficiency could partly dampen the induction of autophagy. Moreover, Notch1 deficiency may lead to the inactivation of p38 and the reduction of β-catenin expression in the Notch1+/− RUN group. In conclusion, Notch1 plays a critical role in physiologic cardiac hypertrophy through the p38 signaling pathway. Our results will help to understand the underlying mechanism of Notch1 on physiological cardiac hypertrophy.

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“…In unstimulated cells, non-phosphorylated cytoplasmic β-catenin translocated/ accumulated within the nucleus to enable downstream gene regulatory activity (26,27). Recently, a series of investigations indicated that the activation of the Wnt/β-catenin signaling pathway contributes to liver injury induced by alcohol consumption (13), and its downregulation increased the levels of proteins involved in glucose aerobic metabolism and β-oxidation in a mouse swimming training model (28). The above data demonstrate that the Wnt/β-catenin signaling pathway plays an important role in inflammation and metabolism, though the involvement of Wnt/β-catenin signaling in lipid metabolism and the inflammatory response of the liver remains uncertain.…”

Section: Discussionmentioning

confidence: 99%

Y-box binding protein 1 regulates liver lipid metabolism by regulating the Wnt/β-catenin signaling pathway

Ma¹,

Zhu²,

Wang³

et al. 2021

Ann Transl Med

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Background: We mainly investigated how y-box binding protein 1 (YB-1) regulates liver lipid metabolism through the Wnt/β-catenin signaling pathway using multiple models.Methods: The LO2 cells were treated with palmitic acid (PA) to create an NAFLD model in vitro.Immunohistochemistry and Western blotting assays were used to detect the expression of YB-1, β-Catenin, SREBP-1c, LXRa, FXR1 and PPARα protein, and RNAs of them was detected by qRT-PCR. Oil Red O assay was applied to observe lipid droplets in LO2 cells and liver tissues. H&E staining was performed to observe the degree of liver inflammation. Proteomics in LO2 cells were conducted by Tandem mass tag proteomics assay. Co-immunoprecipitation and Western blotting assays were used to verify YB-1 complexed pGSK3β.ELISA and Western blotting assays were used to detect the concentrations of TNFα and IL-6 in supernates of LO2 cells and liver tissues, respectively.Results: We found that YB-1 and β-catenin were highly expressed in the LO2 cell NAFLD model, and that the expression of TNFα and IL-6 also increased. Lipid synthases (SREBP-1c and LXRa) expression were decreased, while β-oxidation-related factors (FXR1 and PPARα) expression were increased. The expression of SREBP-1c and LXRa were increased while FXR1 and PPARα were decreased, though such responses were rescued through inhibiting β-catenin expression. Finally, tandem mass tag proteomics, coimmunoprecipitation, and Western blotting demonstrated that YB-1 could form a protein complex with phosphorylated glycogen synthase kinase 3 beta (pGSK3β) to regulate Wnt/β-catenin. In mouse NAFLD livers, immunohistochemistry and Western blotting validated the finding of YB-1 gene downregulation leading to the inhibition of Wnt/β-catenin pathway activation, ultimately inhibiting lipid synthesis and reducing the inflammatory response. Similar to the in vitro investigation, β-catenin overexpression reversed such YB-1 downregulation-induced downstream effects. Upregulation of the YB-1 gene promoted the activation of the Wnt/β-catenin pathway, thus increasing lipid synthesis and the inflammatory response.However, downregulation of β-catenin reversed this phenomenon caused by upregulating YB-1.Conclusions: In summary, these results demonstrate that YB-1 regulates liver lipid metabolism by regulating the Wnt/β-catenin signaling pathway.

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β-Catenin Regulates Cardiac Energy Metabolism in Sedentary and Trained Mice

Cited by 9 publications

References 57 publications

WNT/β‐catenin pathway is a key regulator of cardiac function and energetic metabolism

WNT/β‐catenin pathway is a key regulator of cardiac function and energetic metabolism

Notch1 Is Involved in Physiologic Cardiac Hypertrophy of Mice via the p38 Signaling Pathway after Voluntary Running

Y-box binding protein 1 regulates liver lipid metabolism by regulating the Wnt/β-catenin signaling pathway

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