Functional study of amine oxidase copper-containing 1 (AOC1) in lipid metabolism_Journal of Biomedical Engineering

Authors：

XIANG Siting , LIU Shenying , LI Kuangzheng , ZHAO Tongjin ,  WANG Xu

Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200438, P. R. China;

Corresponding author：

WANG Xu, Email: wangxu@ahmu.edu.cn

Keywords：

Amine oxidase copper-containing 1; Lipid metabolism; Obesity model

DOI：

10.7507/1001-5515.202407066

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Amine oxidase copper-containing 1 (AOC1) is a key member of copper amine oxidase family, which is responsible for deamination oxidation of histamine and putrescine. In recent years, AOC1 has been reported to be associated with various cancers, with its expression levels significantly elevated in certain cancer cells, suggesting its potential role in cancer progression. However, its function in lipid metabolism still remains unclear. Through genetic analysis, we have discovered a potential relationship between AOC1 and lipid metabolism. To further investigate, we generated Aoc1^−/− mice and characterized their metabolic phenotypes on both chow diet and high-fat diet (HFD) feeding conditions. On HFD feeding conditions, Aoc1^−/− mice exhibited significantly higher fat mass and impaired glucose sensitivity, and lipid accumulation in white adipose tissue and liver was also increased. This study uncovers the potential role of AOC1 in lipid metabolism and its implications in metabolic disorders such as obesity and type 2 diabetes, providing new targets and research directions for treating metabolic diseases.

1.	Klema V J, Wilmot C M. The role of protein crystallography in defining the mechanisms of biogenesis and catalysis in copper amine oxidase. Int J Mol Sci, 2012, 13(5): 5375-5405.
2.	Schwelberger H G. The origin of mammalian plasma amine oxidases. J Neural Transm, 2007, 114(6): 757-762.
3.	Enrique-Tarancón G, Marti L, Morin N, et al. Role of semicarbazide-sensitive amine oxidase on glucose transport and GLUT4 recruitment to the cell surface in adipose cells. J Biol Chem, 1998, 273(14): 8025-8032.
4.	Manzotti G, Breda D, Di Gioacchino M, et al. Serum diamine oxidase activity in patients with histamine intolerance. Int J Immunopathol Pharmacol, 2016, 29(1): 105-111.
5.	Ding Q, Lin D, Zhou Y, et al. Downregulation of amine oxidase copper containing 1 inhibits tumor progression by suppressing IL-6/JAK/STAT3 pathway activation in hepatocellular carcinoma. Oncol Lett, 2021, 22(6): 857-863.
6.	Xu F, Xu Y, Xiong J H, et al. AOC1 contributes to tumor progression by promoting the AKT and EMT pathways in gastric cancer. Cancer Manag Res, 2020, 12: 1789-1798.
7.	Vakal S, Jalkanen S, Dahlström K M, et al. Human copper-containing amine oxidases in drug design and development. Molecules, 2020, 25(6): 1293-1322.
8.	Costanzo M C, von Grotthuss M, Massung J, et al. The type 2 diabetes knowledge portal: an open access genetic resource dedicated to type 2 diabetes and related traits. Cell Metab, 2023, 35(4): 695-710.
9.	Dornbos P, Singh P, Jang D K, et al. Evaluating human genetic support for hypothesized metabolic disease genes. Cell Metab, 2022, 34(5): 661-666.
10.	Ibrahim M M. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev, 2010, 11(1): 11-18.
11.	Samuel V T, Shulman G I. Mechanisms for insulin resistance: common threads and missing links. Cell, 2012, 148(5): 852-871.
12.	Shi Y, Burn P. Lipid metabolic enzymes: emerging drug targets for the treatment of obesity. Nat Rev Drug Discov, 2004, 3(8): 695-710.
13.	Holbert C E, Cullen M T, Casero R A, et al. Polyamines in cancer: integrating organismal metabolism and antitumour immunity. Nat Rev Cancer, 2022, 22(8): 467-480.
14.	Liu F, Ou W, Tang W, et al. Increased AOC1 expression promotes cancer progression in colorectal cancer. Front Oncol, 2021, 11: 657210.
15.	Ding Y, Feng Y, Huang Z, et al. SOX15 transcriptionally increases the function of AOC1 to modulate ferroptosis and progression in prostate cancer. Cell Death Dis, 2022, 13(8): 673.
16.	Zheng W H, Long Z Q, Zheng Z Q, et al. m6A-enriched lncRNA LINC00839 promotes tumor progression by enhancing TAF15-mediated transcription of amine oxidase AOC1 in nasopharyngeal carcinoma. J Biol Chem, 2023, 299(7): 104873.
17.	Karer M, Rager-Resch M, Haider T, et al. Diamine oxidase knockout mice are not hypersensitive to orally or subcutaneously administered histamine. Inflamm Res, 2022, 71(4): 497-511.
18.	Ji Y, Sakata Y, Li X, et al. Lymphatic diamine oxidase secretion stimulated by fat absorption is linked with histamine release. Am J Physiol Gastrointest Liver Physiol, 2013, 304(8): G732-G740.
19.	Branco A C C C, Yoshikawa F S Y, Pietrobon A J, et al. Role of histamine in modulating the immune response and inflammation. Mediators Inflamm, 2018, 2018: 9524075.
20.	Hariharan R, Odjidja E N, Scott D, et al. The dietary inflammatory index, obesity, type 2 diabetes, and cardiovascular risk factors and diseases. Obes Rev, 2022, 23(1): e13349.
21.	Hotamisligil G S. Inflammation and metabolic disorders. Nature, 2006, 444(7121): 860-867.
22.	Chen J, Jiang Y, Shi H, et al. The molecular mechanisms of copper metabolism and its roles in human diseases. Pflugers Arch, 2020, 472(10): 1415-1429.
23.	Blades B, Ayton S, Hung Y H, et al. Copper and lipid metabolism: a reciprocal relationship. Biochim Biophys Acta Gen Subj, 2021, 1865(11): 129979.
24.	Morrell A, Tallino S, Yu Lei, et al. The role of insufficient copper in lipid synthesis and fatty-liver disease. IUBMB Life, 2017, 69(4): 263-270.
25.	Burkhead J L, Lutsenko S. The role of copper as a modifier of lipid metabolism// Rodrigo Valenzuela B. Lipid Metabolism. London: InTech, 2013: 39-60.
26.	Krishnamoorthy L, Cotruvo J A, Chan J, et al. Copper regulates cyclic-AMP-dependent lipolysis. Nat Chem Biol, 2016, 12(8): 586-592.
27.	Yang H, Liu C N, Wolf R M, et al. Obesity is associated with copper elevation in serum and tissues. Metallomics, 2019, 11(8): 1363-1371.
28.	Yang H, Ralle M, Wolfgang M J, et al. Copper-dependent amino oxidase 3 governs selection of metabolic fuels in adipocytes. PLoS Biol, 2018, 16(9): e2006519.
29.	Carpéné C, Viana P, Iffiú-Soltesz Z, et al. Effects of chemical structures interacting with amine oxidases on glucose, lipid and hydrogen peroxide handling by human adipocytes. Molecules, 2022, 27(19): 6224.

1. Klema V J, Wilmot C M. The role of protein crystallography in defining the mechanisms of biogenesis and catalysis in copper amine oxidase. Int J Mol Sci, 2012, 13(5): 5375-5405.
2. Schwelberger H G. The origin of mammalian plasma amine oxidases. J Neural Transm, 2007, 114(6): 757-762.
3. Enrique-Tarancón G, Marti L, Morin N, et al. Role of semicarbazide-sensitive amine oxidase on glucose transport and GLUT4 recruitment to the cell surface in adipose cells. J Biol Chem, 1998, 273(14): 8025-8032.
4. Manzotti G, Breda D, Di Gioacchino M, et al. Serum diamine oxidase activity in patients with histamine intolerance. Int J Immunopathol Pharmacol, 2016, 29(1): 105-111.
5. Ding Q, Lin D, Zhou Y, et al. Downregulation of amine oxidase copper containing 1 inhibits tumor progression by suppressing IL-6/JAK/STAT3 pathway activation in hepatocellular carcinoma. Oncol Lett, 2021, 22(6): 857-863.
6. Xu F, Xu Y, Xiong J H, et al. AOC1 contributes to tumor progression by promoting the AKT and EMT pathways in gastric cancer. Cancer Manag Res, 2020, 12: 1789-1798.
7. Vakal S, Jalkanen S, Dahlström K M, et al. Human copper-containing amine oxidases in drug design and development. Molecules, 2020, 25(6): 1293-1322.
8. Costanzo M C, von Grotthuss M, Massung J, et al. The type 2 diabetes knowledge portal: an open access genetic resource dedicated to type 2 diabetes and related traits. Cell Metab, 2023, 35(4): 695-710.
9. Dornbos P, Singh P, Jang D K, et al. Evaluating human genetic support for hypothesized metabolic disease genes. Cell Metab, 2022, 34(5): 661-666.
10. Ibrahim M M. Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev, 2010, 11(1): 11-18.
11. Samuel V T, Shulman G I. Mechanisms for insulin resistance: common threads and missing links. Cell, 2012, 148(5): 852-871.
12. Shi Y, Burn P. Lipid metabolic enzymes: emerging drug targets for the treatment of obesity. Nat Rev Drug Discov, 2004, 3(8): 695-710.
13. Holbert C E, Cullen M T, Casero R A, et al. Polyamines in cancer: integrating organismal metabolism and antitumour immunity. Nat Rev Cancer, 2022, 22(8): 467-480.
14. Liu F, Ou W, Tang W, et al. Increased AOC1 expression promotes cancer progression in colorectal cancer. Front Oncol, 2021, 11: 657210.
15. Ding Y, Feng Y, Huang Z, et al. SOX15 transcriptionally increases the function of AOC1 to modulate ferroptosis and progression in prostate cancer. Cell Death Dis, 2022, 13(8): 673.
16. Zheng W H, Long Z Q, Zheng Z Q, et al. m6A-enriched lncRNA LINC00839 promotes tumor progression by enhancing TAF15-mediated transcription of amine oxidase AOC1 in nasopharyngeal carcinoma. J Biol Chem, 2023, 299(7): 104873.
17. Karer M, Rager-Resch M, Haider T, et al. Diamine oxidase knockout mice are not hypersensitive to orally or subcutaneously administered histamine. Inflamm Res, 2022, 71(4): 497-511.
18. Ji Y, Sakata Y, Li X, et al. Lymphatic diamine oxidase secretion stimulated by fat absorption is linked with histamine release. Am J Physiol Gastrointest Liver Physiol, 2013, 304(8): G732-G740.
19. Branco A C C C, Yoshikawa F S Y, Pietrobon A J, et al. Role of histamine in modulating the immune response and inflammation. Mediators Inflamm, 2018, 2018: 9524075.
20. Hariharan R, Odjidja E N, Scott D, et al. The dietary inflammatory index, obesity, type 2 diabetes, and cardiovascular risk factors and diseases. Obes Rev, 2022, 23(1): e13349.
21. Hotamisligil G S. Inflammation and metabolic disorders. Nature, 2006, 444(7121): 860-867.
22. Chen J, Jiang Y, Shi H, et al. The molecular mechanisms of copper metabolism and its roles in human diseases. Pflugers Arch, 2020, 472(10): 1415-1429.
23. Blades B, Ayton S, Hung Y H, et al. Copper and lipid metabolism: a reciprocal relationship. Biochim Biophys Acta Gen Subj, 2021, 1865(11): 129979.
24. Morrell A, Tallino S, Yu Lei, et al. The role of insufficient copper in lipid synthesis and fatty-liver disease. IUBMB Life, 2017, 69(4): 263-270.
25. Burkhead J L, Lutsenko S. The role of copper as a modifier of lipid metabolism// Rodrigo Valenzuela B. Lipid Metabolism. London: InTech, 2013: 39-60.
26. Krishnamoorthy L, Cotruvo J A, Chan J, et al. Copper regulates cyclic-AMP-dependent lipolysis. Nat Chem Biol, 2016, 12(8): 586-592.
27. Yang H, Liu C N, Wolf R M, et al. Obesity is associated with copper elevation in serum and tissues. Metallomics, 2019, 11(8): 1363-1371.
28. Yang H, Ralle M, Wolfgang M J, et al. Copper-dependent amino oxidase 3 governs selection of metabolic fuels in adipocytes. PLoS Biol, 2018, 16(9): e2006519.
29. Carpéné C, Viana P, Iffiú-Soltesz Z, et al. Effects of chemical structures interacting with amine oxidases on glucose, lipid and hydrogen peroxide handling by human adipocytes. Molecules, 2022, 27(19): 6224.

Journal of Biomedical Engineering

Latest ArticlesFunctional study of amine oxidase copper-containing 1 (AOC1) in lipid metabolism

Abstract Full text Figures/Tables Video References Cited by

Format

Content