SIRT6 Promotes Hepatic Beta-Oxidation via Activation of PPARα

Naiman, Shoshana; Huynh, Frank K.; Gil, Reuven; Glick, Yaïr; Shahar, Yael; Touitou, Noga; Nahum, Liat; Avivi, Matan Y.; Roichman, Asael; Kanfi, Yariv; Gertler, Asaf A.; Doniger, Tirza; Ilkayeva, Olga; Abramovich, Ifat; Yaron, Orly; Lerrer, Batia; Gottlieb, Eyal; Harris, Robert A.; Gerber, Doron; Hirschey, Matthew D.; Cohen, Haim Y.

doi:10.1016/j.celrep.2019.11.067

Cited by 80 publications

(83 citation statements)

References 86 publications

(99 reference statements)

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“…SIRT3 has a role in mitochondrial fatty-acid β-oxidation by regulating long-chain acyl-CoA dehydrogenase (LCAD) ( Hirschey et al, 2010 ). SIRT6 is indispensable for hepatic β-oxidation by deacetylating the peroxisome proliferator-activated receptor α (PPARα) coactivator nuclear receptor coactivator 2 (NCOA2) at K780 ( Naiman et al, 2019 ). Following palmitic acid treatment, SIRT6 interacts with p53 to regulate de novo cardiolipin biosynthesis and maintain lipid homeostasis ( Li et al, 2018 ).…”

Section: Biological Functions Of Hdacsmentioning

confidence: 99%

The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy

Guo

Tian

Zhu

2020

Front. Cell Dev. Biol.

199

135

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Genetic mutations and abnormal gene regulation are key mechanisms underlying tumorigenesis. Nucleosomes, which consist of DNA wrapped around histone cores, represent the basic units of chromatin. The fifth amino group (N ε) of histone lysine residues is a common site for post-translational modifications (PTMs), and of these, acetylation is the second most common. Histone acetylation is modulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), and is involved in the regulation of gene expression. Over the past two decades, numerous studies characterizing HDACs and HDAC inhibitors (HDACi) have provided novel and exciting insights concerning their underlying biological mechanisms and potential anti-cancer treatments. In this review, we detail the diverse structures of HDACs and their underlying biological functions, including transcriptional regulation, metabolism, angiogenesis, DNA damage response, cell cycle, apoptosis, protein degradation, immunity and other several physiological processes. We also highlight potential avenues to use HDACi as novel, precision cancer treatments.

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Section: Biological Functions Of Hdacsmentioning

confidence: 99%

The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy

Guo

Tian

Zhu

2020

Front. Cell Dev. Biol.

199

135

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“…Trans-10, cis-12 conjugated linoleic acid can change fat metabolism in goat mammary epithelial cells through AMPK signaling pathway [9]. SIRT6, as a downstream regulator of AMPK, can also effectively inhibit body fat deposition [36]. In this study, Kp-10 signi cantly inhibited the phosphorylation level of AMPK and the expression of SIRT6.…”

Section: Discussionmentioning

confidence: 52%

Kisspeptin-10 Promoting the Synthesis of Milk Fat by Inhibiting the AMPK/SIRT6 Signaling Pathway via the GPR54 in Bovine Mammary Epithelial Cells

Cao

Liu

Zhang

et al. 2020

Preprint

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Background Kp-10 is a peptide hormone mainly involved in the initiation tissue development in puberty. Recent studies have shown that Kp-10 is involved in fat synthesis. However, the role of Kp-10 in milk fat synthesis in lactating dairy cows has not been reported. Therefore, this study investigated the correlation between GPR54 and milk fat synthesis in dairy cows and to study the underlying mechanism in BMECs. Results The results showed that the expression of GPR54, SREBP1 and FASN in mammary glands of high-milk fat dairy cows were significantly higher than those in mammary glands of low-milk fat dairy cows. Meanwhile, 10nM Kp-10 can significantly inhibit AMPK/SIRT6 signaling pathway and promote milk fat synthesis in BMECs through its receptor GPR54. Overexpression of SIRT6 significantly reduced the acetylation level of SREBP1 and milk fat synthesis in BMECs.Conclusions These results suggested that Kp-10 inhibits the AMPK / SIRT6 signaling pathway by mediating GPR54, thereby increasing SREBP1 acetylation levels and increasing milk fat synthesis in BMECs.

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“…In addition, SIRT6 can promote hepatic FA β‐oxidation and inhibit pyruvate oxidation through activating PPAR‐α by binding to PPAR‐α coactivator NCOA2 and decreasing its acetylation. Through this manner, SIRT6 properly regulates the whole‐body respiratory exchange ratio and liver fat content, thereby preventing from fatty liver and other metabolic dysregulation diseases 259 . Consistent with this finding, SIRT6 and miR‐122 negatively regulate each other to coregulate the FA β‐oxidation 260 .…”

Section: Human Diseasesmentioning

confidence: 56%

Emerging roles of SIRT6 in human diseases and its modulators

Liu

Chen

Liu

et al. 2020

Medicinal Research Reviews

103

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The biological functions of sirtuin 6 (SIRT6; e.g., deacetylation, defatty‐acylation, and mono‐ADP‐ribosylation) play a pivotal role in regulating lifespan and several fundamental processes controlling aging such as DNA repair, gene expression, and telomeric maintenance. Over the past decades, the aberration of SIRT6 has been extensively observed in diverse life‐threatening human diseases. In this comprehensive review, we summarize the critical roles of SIRT6 in the onset and progression of human diseases including cancer, inflammation, diabetes, steatohepatitis, arthritis, cardiovascular diseases, neurodegenerative diseases, viral infections, renal and corneal injuries, as well as the elucidation of the related signaling pathways. Moreover, we discuss the advances in the development of small molecule SIRT6 modulators including activators and inhibitors as well as their pharmacological profiles toward potential therapeutics for SIRT6‐mediated diseases.

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SIRT6 Promotes Hepatic Beta-Oxidation via Activation of PPARα

Cited by 80 publications

References 86 publications

The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy

The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy

Kisspeptin-10 Promoting the Synthesis of Milk Fat by Inhibiting the AMPK/SIRT6 Signaling Pathway via the GPR54 in Bovine Mammary Epithelial Cells

Emerging roles of SIRT6 in human diseases and its modulators

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