SIRT6 regulates SREBP1c-induced glucolipid metabolism in liver and pancreas via the AMPKα-mTORC1 pathway

Bian, Che; Zhang, Haibo; Gao, Jing; Wang, Yuxia; Li, Jia; Guo, Dan; Wang, Wei; Song, Yiyun; Weng, Yang; Ren, Huiwen

doi:10.1038/s41374-021-00715-1

Cited by 20 publications

(14 citation statements)

References 39 publications

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“…41,42 Moreover, PPAR-α and SREBP1-c, i.e., the major genes controlling fatty acid synthesis and oxidation, regulate the hepatic lipid metabolism in ALD. 14,15 Interestingly, SIRT6 improves glucose and lipid metabolism by regulating PPAR-α and SREBP1-c. 40,68 After observing H&E-and Oil Red O-stained slides and measuring the expression of β-oxidationand lipid synthesis-related genes, we found that ginsenoside Rc reversed alcohol-induced hepatic steatosis. In keeping with our findings, the ginsenoside Rcinduced mitigation of lipid accumulation was abolished by SIRT6's deficiency.…”

Section: ■ Discussionmentioning

confidence: 90%

“…Reports indicate that under the action of hepatic drug-metabolizing enzymes, alcohol induces the generation of free radicals, which consume the antioxidants present in liver cells, causing the rapid accumulation of large amounts of TG in the same cells and, hence, liver steatosis. , Moreover, PPAR-α and SREBP1-c, i.e., the major genes controlling fatty acid synthesis and oxidation, regulate the hepatic lipid metabolism in ALD. , Interestingly, SIRT6 improves glucose and lipid metabolism by regulating PPAR-α and SREBP1-c. , After observing H&E- and Oil Red O-stained slides and measuring the expression of β-oxidation- and lipid synthesis-related genes, we found that ginsenoside Rc reversed alcohol-induced hepatic steatosis. In keeping with our findings, the ginsenoside Rc-induced mitigation of lipid accumulation was abolished by SIRT6’s deficiency.…”

Section: Discussionmentioning

confidence: 99%

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Ginsenoside Rc Modulates SIRT6-NRF2 Interaction to Alleviate Alcoholic Liver Disease

Pan

Guo

Tang

et al. 2022

J. Agric. Food Chem.

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Alcoholic liver disease (ALD) is a serious worldwide health problem. Ginsenoside Rc is a major active ingredient isolated from Panax ginseng, whose pharmacological effects counteract oxidative stress, inflammation, and lipid accumulation. However, it is still unclear whether ginsenoside Rc might exert beneficial effects on alcohol-induced liver injury. To this aim, mice primary hepatocytes (MPHs) were challenged with alcohol to test ginsenoside Rc’s effects on their intracellular alcohol metabolism. C57BL/6J mice or SIRT6alb–/– mice were chronically fed a diet with added alcohol or given a single gavage of alcohol with or without ginsenoside Rc. Analyses of alcohol metabolism, oxidative stress, inflammation, lipid metabolism, and RNaseq expression were conducted to explore potential targets exploited by ginsenoside Rc to protect against ALD. Our results showed that ginsenoside Rc attenuated alcohol-induced liver injury by regulating oxidative stress, inflammation, and lipid accumulation both in vivo and in vitro. Ginsenoside Rc did increase the deacetylase activity of SIRT6, thereby lowering acetylated NRF2 levels, which elevated NRF2’s stability, and subsequently exerting an antioxidant effect. In keeping with this, the hepatic knockout of SIRT6 almost abolished the hepatoprotective effects of ginsenoside Rc against ALD. Therefore, our results suggest that ginsenoside Rc attenuated hepatocytes’ damage and oxidative stress in ALD by up-regulating the SIRT6/NRF2 pathway. Hence, ginsenoside Rc may be a promising drug to treat or relieve ALD.

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Section: ■ Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rc Modulates SIRT6-NRF2 Interaction to Alleviate Alcoholic Liver Disease

Pan

Guo

Tang

et al. 2022

J. Agric. Food Chem.

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“…Sirtuins are other regulators slowing cell and organism aging [ 42 , 43 , 44 ], although the precise mechanisms by which this is attained are unclear. Sirtuins can modulate cell metabolic state and proteostasis at different levels [ 42 , 45 , 46 , 47 , 48 ], as well as counteract genome reprogramming [ 49 , 50 ]. Sirtuins were proven to exert an anti-aging effect on skin components, reducing inflammaging and promoting autophagy [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

SCA® Slows the Decline of Functional Parameters Associated with Senescence in Skin Cells

Castro

Paz

González

et al. 2022

IJMS

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The identification of compounds and natural ingredients that can counteract tissue stress and dysfunction induced by aging in skin cells is warranted. Here, we investigated the activity of the secretion from the snail Cryptomphalus aspersa (SCA®), an active compound with well-established beneficial effects on skin integrity and aging. To determinate its senescence-regulation mechanisms, we used a model where damage was induced by hydrogen peroxide (H2O2). The results showed that SCA® positively modulated factors involved in cell senescence such as β-galactosidase and cell morphology, secretory efficiency markers (SIRT1/6 and carboxymethyl-lysine), and metabolic and redox homeostasis (mTOR and ROS). This study demonstrated a novel compound that is activity-modulating, reduces cell senescence, and increases longevity to maintain skin homeostasis and functionality.

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“…AMPK is a key molecule in the regulation of biological energy metabolism. Our previous research found that SIRT6 regulated sterol regulatory element-binding protein 1c mediated glucolipid metabolism in the liver and pancreas through AMPKα-mTORC1 ( 147 ). In the DKD study, SIRT1 regulated podocyte fatty acid synthesis via AMPK-SREBP1 ( 92 ), podocyte inflammation by AMPK-NFκB ( 90 ), glucolipid metabolism, and mitochondrial function by AMPK-PGC1α ( 82 ), fibronectin in mesangial matrix deposition ( 94 ), and protein synthesis and mesangial cell hypertrophy through AMPK-mTOR ( 97 ).…”

Section: Role Of the Sirtuin Family In Diabetic Kidney Diseasementioning

confidence: 99%

Sirtuin Family and Diabetic Kidney Disease

Bian

Ren

2022

Front. Endocrinol.

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Diabetes mellitus (DM) is gradually attacking the health and life of people all over the world. Diabetic kidney disease (DKD) is one of the most common chronic microvascular complications of DM, whose mechanism is complex and still lacks research. Sirtuin family is a class III histone deacetylase with highly conserved NAD+ binding domain and catalytic functional domain, while different N-terminal and C-terminal structures enable them to bind different deacetylated substrates to participate in the cellular NAD+ metabolism. The kidney is an organ rich in NAD+ and database exploration of literature shows that the Sirtuin family has different expression localization in renal, cellular, and subcellular structures. With the progress of modern technology, a variety of animal models and reagents for the Sirtuin family and DKD emerged. Machine learning in the literature shows that the Sirtuin family can regulate pathophysiological injury mainly in the glomerular filtration membrane, renal tubular absorption, and immune inflammation through various mechanisms such as epigenetics, multiple signaling pathways, and mitochondrial function. These mechanisms are the key nodes participating in DKD. Thus, it is of great significance for target therapy to study biological functions of the Sirtuin family and DKD regulation mechanism in-depth.

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SIRT6 regulates SREBP1c-induced glucolipid metabolism in liver and pancreas via the AMPKα-mTORC1 pathway

Cited by 20 publications

References 39 publications

Ginsenoside Rc Modulates SIRT6-NRF2 Interaction to Alleviate Alcoholic Liver Disease

Ginsenoside Rc Modulates SIRT6-NRF2 Interaction to Alleviate Alcoholic Liver Disease

SCA® Slows the Decline of Functional Parameters Associated with Senescence in Skin Cells

Sirtuin Family and Diabetic Kidney Disease

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