The Role of Palmitoleic Acid in Regulating Hepatic Gluconeogenesis through SIRT3 in Obese Mice

Guo, Xin; Jiang, Xiaofan; Chen, Keyun; Liang, Qijian; Zhang, Shixiu; Zheng, Juan; Ma, Xiaomin; Jiang, Hongmei; Wu, Hao; Tong, Qiang

doi:10.3390/nu14071482

Cited by 17 publications

(12 citation statements)

References 54 publications

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“…Another explanation is that the high-fat diet Relative mRNA levels supplemented with high fructose/glucose in drinking water might suppress PCK1 expression 34 . Under a high-fat diet, PA decreased PCK1 expression via SIRT3 inhibition 35 . Additionally, acetylation, ubiquitination, and phosphorylation modulate PCK1 expression 36 .…”

Section: Discussionmentioning

confidence: 99%

Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K/AKT/PDGF axis activation in male mice

Liu

Zhang

et al. 2023

Nat Commun

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Metabolic associated fatty liver disease (MAFLD) encompasses a broad spectrum of hepatic disorders, including steatosis, nonalcoholic steatohepatitis (NASH) and fibrosis. We demonstrated that phosphoenolpyruvate carboxykinase 1 (PCK1) plays a central role in MAFLD progression. Male mice with liver Pck1 deficiency fed a normal diet displayed hepatic lipid disorder and liver injury, whereas fibrosis and inflammation were aggravated in mice fed a high-fat diet with drinking water containing fructose and glucose (HFCD-HF/G). Forced expression of hepatic PCK1 by adeno-associated virus ameliorated MAFLD in male mice. PCK1 deficiency stimulated lipogenic gene expression and lipid synthesis. Moreover, loss of hepatic PCK1 activated the RhoA/PI3K/AKT pathway by increasing intracellular GTP levels, increasing secretion of platelet-derived growth factor-AA (PDGF-AA), and promoting hepatic stellate cell activation. Treatment with RhoA and AKT inhibitors or gene silencing of RhoA or AKT1 alleviated MAFLD progression in vivo. Hepatic PCK1 deficiency may be important in hepatic steatosis and fibrosis development through paracrine secretion of PDGF-AA in male mice, highlighting a potential therapeutic strategy for MAFLD.

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Section: Discussionmentioning

confidence: 99%

Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K/AKT/PDGF axis activation in male mice

Liu

Zhang

et al. 2023

Nat Commun

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“…Through sequencing, we screened MDH2 as a target for deacetylation by SIRT3, and in combination with IP experiments, we demonstrated that Sirt3 directly deacetylates MDH2. Hence, SIRT3 is able to directly communicate and alter the acetylation level of MDH2 (60,61) . Our research confirms this conclusion.…”

Section: Discussionmentioning

confidence: 99%

Intermittent fasting promotes adipocyte mitochondrial fusion through Sirt3-mediated deacetylation of Mdh2

Liang

Tian

et al. 2023

Br J Nutr

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Fat deposition and lipid metabolism are closely related to the morphology, structure and function of mitochondria. The morphology of mitochondria between fusion and fission processes is mainly regulated by protein posttranslational modification (PTM). Intermittent fasting (IF) promotes high expression of Sirtuin 3 (Sirt3) and induces mitochondrial fusion in high-fat diet (HFD)-fed mice. However, the mechanism by which Sirt3 participates in mitochondrial protein acetylation during IF to regulate mitochondrial fusion and fission dynamics remains unclear. This article demonstrates that IF promotes mitochondrial fusion and improves mitochondrial function in HFD mouse inguinal white adipose tissue (iWAT). Proteomic sequencing revealed that IF increased protein deacetylation levels in HFD mice and significantly increased Sirt3 mRNA and protein expression. After transfecting with Sirt3 overexpression or interference vectors into adipocytes, we found that Sirt3 promoted adipocyte mitochondrial fusion and improved mitochondrial function. Furthermore, Sirt3 regulates the JNK-FIS1 pathway by deacetylating malate dehydrogenase 2 (MDH2) to promote mitochondrial fusion. In summary, our study indicates that IF promotes mitochondrial fusion and improves mitochondrial function by upregulating the high expression of Sirt3 in HFD mice, promoting deacetylation of MDH2, and inhibiting the JNK-FIS1 pathway. This research provides theoretical support for studies related to energy limitation and animal lipid metabolism.

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“…Lysates prepared from frozen liver samples were used for western blot. The level of phospho-NF-κB p65 (Ser536) (Cell Signaling Technology, #3033), NFκB p65 (Cell Signaling Technology, #8214), the stress-activated protein kinase/Jun-amino-terminal kinase (SAPK/JNK) (Cell Signaling Technology, #9252), phospho-SAPK/JNK(Thr183/Thr185) (Cell Signaling Technology, #9251), IL-1β (Cell Signaling Technology, #12242), Phospho-p38 MAPK (Thr180/Tyr182) (Cell Signaling Technology, #4511), p38 MAPK (Cell Signaling Technology, #8690), FGF21 (Affinity Biosciences, #DF8947), Collagen 1 a 1 (Santa Cruz Biotechnology, # sc-293182),Collagen 3 a 1 (Santa Cruz Biotechnology, #sc-271249), Smooth muscle ac-tin (Santa Cruz Biotechnology, #sc-53142) and Tubulin (Cell Signaling Technology, #2125) were analyzed as described ( 25 , 26 ).…”

Section: Methodsmentioning

confidence: 99%

Theabrownin ameliorates liver inflammation, oxidative stress, and fibrosis in MCD diet-fed C57BL/6J mice

Zhen

Liang²,

Wang³

et al. 2023

Front. Endocrinol.

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IntroductionNonalcoholic steatohepatitis (NASH), also known as metabolic steatohepatitis, is a clinical syndrome with pathological changes like alcoholic hepatitis but without a history of excessive alcohol consumption. NASH is closely related to metabolic disorders such as obesity, insulin resistance, type 2 diabetes mellitus, and hyperlipidemia. Its main characteristics are hepatocyte steatosis with hepatocyte injury and inflammation. In severe cases, it can develop into liver cirrhosis. At present, there is no special treatment for NASH. Theabrownin (TB) is the main pigment substance in fermented tea. Theabrownin has beneficial effects on lipid metabolism and intestinal flora. However, the effect of theabrownin on NASH has not been studied. MethodsThis study was aimed at exploring the effects of theabrownin from Fuzhuan brick tea on NASH. 8-week-old mice were randomly assigned to three groups and fed with chow diet (CD), methionine and choline sufficient (MCS) diet (MCS Ctrl), which is a Methionine/choline deficient (MCD) control diet, and MCD diet. After 5 weeks of feeding, the MCD group mice were randomly divided into two groups and were gavaged with double distilled water (MCD Ctrl) or theabrownin (MCD TB) (200mg/kg body weight, dissolved in double distilled water) every day for another 4 weeks respectively, while continuing MCD diet feeding.ResultsWe found that theabrownin treatment could not improve liver mass loss and steatosis. However, theabrownin ameliorated liver injury and decreased liver inflammatory response. Theabrownin also alleviated liver oxidative stress and fibrosis. Furthermore, our results showed that theabrownin increased hepatic level of fibroblast growth factor 21 (FGF21) and reduced the phosphorylation of mitogen-activated protein kinase p38 in MCD diet-fed mice.

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The Role of Palmitoleic Acid in Regulating Hepatic Gluconeogenesis through SIRT3 in Obese Mice

Cited by 17 publications

References 54 publications

Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K/AKT/PDGF axis activation in male mice

Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K/AKT/PDGF axis activation in male mice

Intermittent fasting promotes adipocyte mitochondrial fusion through Sirt3-mediated deacetylation of Mdh2

Theabrownin ameliorates liver inflammation, oxidative stress, and fibrosis in MCD diet-fed C57BL/6J mice

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