Protective effects of 5-heptadecylresorcinol against adipocyte mitochondrial dysfunction through upregulation of Sirt3-mediated autophagy

Hao, Yiming; Yang, Zihui; Liu, Jie; Wang, Ziyuan; Speakman, John R.; Niu, Chaoqun; Sun, Baoguo

doi:10.1016/j.jnutbio.2022.108956

Cited by 13 publications

(21 citation statements)

References 30 publications

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“…The results showed that the protein and mRNA expressions of UCP1 and PGC1α in BAC and 3T3-L1 adipocytes were significantly decreased after 3-TYP administration, and the promotional effects of AR-C17 on the expressions of UCP1 and PGC1α were almost abolished under 3-TYP administration (Figures and S7). Meanwhile, the protein and mRNA expressions of Sirt3 were slightly decreased by 3-TYP (Figures and S7), which were consistent with a previous study . Therefore, Sirt3 was required for the AR-C17-induced thermogenesis in BAC and 3T3-L1 adipocytes, and Sirt3 might be a target of AR-C17 in thermogenic adipocytes.…”

Section: Resultssupporting

confidence: 90%

“…Meanwhile, the protein and mRNA expressions of Sirt3 were slightly decreased by 3-TYP (Figures 7 and S7), which were consistent with a previous study. 32 Therefore, Sirt3 was required for the AR-C17-induced thermogenesis in BAC and 3T3-L1 adipocytes, and Sirt3 might be a target of AR-C17 in thermogenic adipocytes.…”

Section: Influence Of Ar-c17 On Thermogenesis Of Aging Adipocytes In ...mentioning

confidence: 95%

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5-Heptadecylresorcinol Regulates the Metabolism of Thermogenic Fat and Improves the Thermogenic Capacity of Aging Mice via a Sirtuin 3–Adenosine Monophosphate-Activated Protein Kinase Pathway

Zhang

et al. 2022

J. Agric. Food Chem.

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5-Heptadecylresorcinol (AR-C17), a well-known biomarker for whole grain rye consumption, is a primary homolog of alkylresorcinols. In this study, the effects of AR-C17 on the thermogenesis of brown adipocytes and 3T3-L1 adipocytes were investigated. The results showed that AR-C17 increased sirtuin 3 (Sirt3) expression, and the expressions of specific thermogenic genes in adipocytes were increased. Furthermore, AR-C17 increased the mitochondrial functions during the thermogenic activation of adipocytes. In in vivo study, AR-C17 increased the cold tolerance and thermogenic capacity of adipose tissues in aging mice. In addition, Sirt3 activity was required for AR-C17-induced thermogenesis. Meanwhile, AR-C17 increased adenosine monophosphateactivated protein kinase (AMPK) phosphorylation, and AMPK was involved in the regulation of AR-C17 on thermogenic adipocytes. Mechanically, AR-C17 upregulated a Sirt3−AMPK positive-feedback loop in adipocytes and further increased the expression of uncoupling protein 1 to activate thermogenesis. This study indicated that AR-C17 could be a promising thermogenic activator of adipocytes to alleviate obesity and aging-associated metabolic diseases.

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Section: Resultssupporting

confidence: 90%

Section: Influence Of Ar-c17 On Thermogenesis Of Aging Adipocytes In ...mentioning

confidence: 95%

5-Heptadecylresorcinol Regulates the Metabolism of Thermogenic Fat and Improves the Thermogenic Capacity of Aging Mice via a Sirtuin 3–Adenosine Monophosphate-Activated Protein Kinase Pathway

Zhang

et al. 2022

J. Agric. Food Chem.

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“…[67][68][69] Notably, FOXO3a, ATG7, and Beclin-1 are also important targets of AR-C17 in regulating autophagy. 22,48,53 EP300 is also an emerging therapeutic target for prostate and breast cancer, since EP300 (encoding p300) knockdown comprehensively inhibits the expression of estrogen-regulated genes, and a reduction in steroid content would inhibit the growth of such cancers. 70,71 Several studies have found that ARs can inhibit breast cancer and steroid synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…52 AR-C17 can ameliorate mitochondrial dysfunction by increasing autophagy in adipocytes through activating Sirt3. 53 Comparing the targets reported in the above literature (literature-targets) with the captured 163 original targets, four coincident targets were found, which were LC3-II, SOD2, HO-1 (HMOX1) and CYP11A1, respectively.…”

Section: Kegg Pathway Enrichment Analysismentioning

confidence: 95%

Analysis of the multi-physiological and functional mechanism of wheat alkylresorcinols based on reverse molecular docking and network pharmacology

Wei

Wang

et al. 2022

Food Funct.

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“…[ 16 ] It has been proven to be involved in multiple mitochondrial processes, including ATP production, reactive oxygen species (ROS) generation, electron transport chain function, mitochondrial permeability transition pore (mPTP) regulation, and mitochondrial dynamics. [ 17 ] Furthermore, it was revealed to exert notable protective effects against endothelial cell injury, inflammation, and atherosclerotic plaque development. [ 18 ] Whereas, the action mechanism of AR‐C17 in regulating endothelial function mediated by SIRT3 has not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

5‐Heptadecylresorcinol Protects against Atherosclerosis in Apolipoprotein E‐Deficient Mice by Modulating SIRT3 Signaling: The Possible Beneficial Effects of Whole Grain Consumption

Hao

Yang

et al. 2022

Molecular Nutrition Food Res

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Scope Whole grain consumption has been proven to be inversely associated with the risk of cardiovascular diseases. As a biomarker for whole grain dietary intake, 5‐heptadecylresorcinol (AR‐C17) has attracted increased attention due to its potential health‐improving activity. However, the beneficial effect of AR‐C17 on atherosclerosis prevention and the underlying mechanism remain unclear. Methods and Results High‐fat diet fed apolipoprotein E‐deficient (ApoE−/−) mice are administrated with or without AR‐C17 (30 and 150 mg kg−1) for 16 weeks. Histological staining is performed for plaque analysis. Immunofluorescence, western blot, and seahorse cell analysis are carried out to investigate the action of mechanism of AR‐C17. The results indicate that AR‐C17 supplementation lowered serum total cholesterol, triglyceride, VLDL‐C, and LDL‐C levels. Moreover, the atherosclerotic plaques in the aortic root region of mice heart are significantly reduced by AR‐C17 intervention compared with ApoE−/− control group. In addition, AR‐C17 treatment alleviates endothelial cell damage and apoptosis by improving mitochondrial function via sirtuin3 signaling pathway both in ApoE−/− mice and oxidized‐LDL‐treated human umbilical vein endothelial cells. Conclusion AR‐C17 may be applied as a promising grain‐based dietary bioactive ingredient for atherosclerosis prevention. Meanwhile, as a mitochondrial protective agent, it can offer support for the suggested health claim of whole grain diet.

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Protective effects of 5-heptadecylresorcinol against adipocyte mitochondrial dysfunction through upregulation of Sirt3-mediated autophagy

Cited by 13 publications

References 30 publications

5-Heptadecylresorcinol Regulates the Metabolism of Thermogenic Fat and Improves the Thermogenic Capacity of Aging Mice via a Sirtuin 3–Adenosine Monophosphate-Activated Protein Kinase Pathway

5-Heptadecylresorcinol Regulates the Metabolism of Thermogenic Fat and Improves the Thermogenic Capacity of Aging Mice via a Sirtuin 3–Adenosine Monophosphate-Activated Protein Kinase Pathway

Analysis of the multi-physiological and functional mechanism of wheat alkylresorcinols based on reverse molecular docking and network pharmacology

5‐Heptadecylresorcinol Protects against Atherosclerosis in Apolipoprotein E‐Deficient Mice by Modulating SIRT3 Signaling: The Possible Beneficial Effects of Whole Grain Consumption

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