Inhibition of acetyl‑CoA carboxylase by PP‑7a exerts beneficial effects on metabolic dysregulation in a mouse model of diet‑induced obesity
Open accessAbstract
Acetyl-coenzyme A carboxylase (ACC) is a critical regulator of fatty acid metabolism and represents a promising therapeutic target for metabolic diseases, including obesity, type 2 diabetes and non-alcoholic fatty liver disease. Recently, a novel ACC inhibitor, PP-7a, was developed by our group by utilizing a structure-based drug design. In the present study, the pharmacological effects of PP-7a on the metabolic dysregulation in mice with high-fat diet (HFD)-induced obesity and the underlying mechanisms were investigated. The inhibitory effect on ACC activities was confirmed by assessing the level of malonyl-CoA, a product synthesized by the catalyzation of ACC. Following 16 weeks of being fed an HFD, the mice were administered PP-7a (15, 45 or 75 mg/kg) for 4 weeks. The effects of PP-7a on weight gain, glucose intolerance, hepatic lipid accumulation and the increase of serum triglyceride (TG), total cholesterol (TC) and free fatty acids (FFA) in mice were assessed. CP-640186 was used as a positive control drug and administered in the same manner as PP-7a. Chronic administration of PP-7a lowered the malonyl-CoA levels in liver and heart tissues of mice in the HFD group. In addition, HFD-induced weight gain and glucose intolerance were improved by PP-7a treatment in the mice fed the HFD. Furthermore, PP-7a suppressed hepatic lipid accumulation and the increase in TG, TC and FFA levels. Taken together, these results suggest that ACC inhibition by PP-7a may have a beneficial effect on metabolic dysregulation in obese mice.
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Peptides derived from L. platensis inhibit ACC activity, thereby reducing fatty acid synthesis and limiting lipid accumulation in hepatic and adipose tissues.
“Peptides derived from L. platensis inhibit ACC activity, thereby reducing fatty acid synthesis and limiting lipid accumulation in hepatic and adipose tissues [151–153].”
From Navigating the potential of algal peptides: health effects, market applications, and scientific challenges (2026) · cites this paper as [152]
The Results (page not supplied) report that PP-7a reduced liver fat accumulation, adipocyte size and abdominal adipose volume in high-fat-diet-fed mice. The Discussion says ACC inhibition suppresses fatty acid biosynthesis. But the paper studies PP-7a, described as a structure-designed ACC inhibitor, not peptides derived from L. platensis; it does not support attributing these effects to those peptides. (LLM, conf=0.88)
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Cites
High-fat diet-induced obesity in animal models
Hariri, N., & Thibault, L. (2010) · Nutrition Research Reviews · doi:10.1017/s0954422410000168 · Cited by 1,090 · see citing works
Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2
Abu-Elheiga, L., Matzuk, M. M., Abo-Hashema, K. A. H., & Wakil, S. J. (2001) · Science · doi:10.1126/science.1056843 · Cited by 903 · see citing works
Fatty acid metabolism: Target for metabolic syndrome
Wakil, S. J., & Abu-Elheiga, L. A. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r800079-jlr200 · Cited by 731 · see citing works
Fatty acid oxidation and carnitine palmitoyltransferase I: emerging therapeutic targets in cancer
Qu, Q., Zeng, F., Liu, X., Wang, Q. J., & Deng, F. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.132 · Cited by 548 · see citing works
Causes and Metabolic Consequences of Fatty Liver
Stefan, N., Kantartzis, K., & Häring, H. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0009 · Cited by 529 · see citing works
Mechanisms by which Dietary Fatty Acids Modulate Plasma Lipids
Fernandez, M. L., & West, K. L. (2005) · The Journal of Nutrition · doi:10.1093/jn/135.9.2075 · Cited by 469 · see citing works
The subcellular localization of acetyl-CoA carboxylase 2
Abu-Elheiga, L. A., Brinkley, W. R., Zhong, L., Chirala, S. S., Woldegiorgis, G., & Wakil, S. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.4.1444 · Cited by 450 · see citing works
Obesity and Cancer Risk: Recent Review and Evidence
Basen-Engquist, K., & Chang, M. (2011) · Current Oncology Reports · doi:10.1007/s11912-010-0139-7 · Cited by 439 · see citing works
Regulation of acetyl-CoA carboxylase
Brownsey, R. W., Boone, A. N., Elliott, J. E., Kulpa, J. E., & Lee, W. M. (2006) · Biochemical Society Transactions · doi:10.1042/bst20060223 · Cited by 429 · see citing works
Role of free fatty acids in endothelial dysfunction
Ghosh, A., Gao, L., Thakur, A., Siu, P. M., & Lai, C. W. K. (2017) · Journal of Biomedical Science · doi:10.1186/s12929-017-0357-5 · Cited by 420 · see citing works
Kim, C.-W., Addy, C., Kusunoki, J., Anderson, N. N., Deja, S., Fu, X., Burgess, S. C., Li, C., Ruddy, M., Chakravarthy, M., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.07.009 · Cited by 419 · see citing works
Fatty acid metabolism in the regulation of T cell function
Lochner, M., Berod, L., & Sparwasser, T. D. (2015) · Trends in Immunology · doi:10.1016/j.it.2014.12.005 · Cited by 417 · see citing works
Genetic control of de novo lipogenesis: role in diet-induced obesity
Strable, M. S., & Ntambi, J. M. (2010) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409231003667500 · Cited by 415 · see citing works
Acetyl-CoA carboxylase regulation of fatty acid oxidation in the heart.
Saddik, M., Gamble, J., Witters, L. A., & Lopaschuk, G. D. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)74465-2 · Cited by 390 · see citing works
An Overview of Murine High Fat Diet as a Model for Type 2 Diabetes Mellitus
Heydemann, A. (2016) · Journal of Diabetes Research · doi:10.1155/2016/2902351 · Cited by 376 · see citing works
Choi, C. S., Savage, D. B., Abu-Elheiga, L., Liu, Z.-X., Kim, S., Kulkarni, A., Distefano, A., Hwang, Y.-J., Reznick, R. M., Codella, R., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706794104 · Cited by 325 · see citing works
Changes in Plasma Free Fatty Acids Associated with Type-2 Diabetes
Sobczak, A. I. S., Blindauer, C. A., & Stewart, A. J. (2019) · Nutrients · doi:10.3390/nu11092022 · Cited by 306 · see citing works
Regulation of mammalian acetyl-CoA carboxylase
Munday, M. R. (2002) · Biochemical Society Transactions · doi:10.1042/bst0301059 · Cited by 301 · see citing works
Liver disease and diabetes mellitus.
Na, B., Herrine, S. K., & Rubin, R. A. (2001) · PubMed · Cited by 299 · see citing works
Harriman, G., Greenwood, J., Bhat, S., Huang, X., Wang, R., Paul, D., Tong, L., Saha, A. K., Westlin, W. F., Kapeller, R., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520686113 · Cited by 287 · see citing works
Goedeke, L., Bates, J. G., Vatner, D. F., Perry, R. J., Wang, T., Ramírez, R., Li, L., Ellis, M. W., Zhang, D., Wong, K. E., et al. (2018) · Hepatology · doi:10.1002/hep.30097 · Cited by 257 · see citing works
Harwood, H. J., Petras, S. F., Shelly, L. D., Zaccaro, L. M., Perry, D. A., Makowski, M. R., Hargrove, D. M., Martin, K. A., Tracey, W. R., Chapman, J. G., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304481200 · Cited by 242 · see citing works
The role of dietary fat in obesity.
Golay, A., & Bobbioni, E. (1997) · PubMed · Cited by 232 · see citing works
Acetyl-coenzyme A carboxylases: versatile targets for drug discovery
Tong, L., & Harwood, H. J. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21077 · Cited by 207 · see citing works
Free Fatty Acid Levels Modulate Microvascular Function
de Jongh, R. T., Serné, E. H., IJzerman, R. G., de Vries, G., & Stehouwer, C. D. A. (2004) · Diabetes · doi:10.2337/diabetes.53.11.2873 · Cited by 201 · see citing works
Luteolin Protects against High Fat Diet-Induced Cognitive Deficits in Obesity Mice
Liu, Y., Fu, X., Lan, N., Li, S., Zhang, J., Wang, S., Li, C., Shang, Y., Huang, T., & Zhang, L. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.02.040 · Cited by 194 · see citing works
Malonyl-CoA metabolism in cardiac myocytes and its relevance to the control of fatty acid oxidation
Awan, M. M., & SAGGERSON, E. D. (1993) · Biochemical Journal · doi:10.1042/bj2950061 · Cited by 188 · see citing works
Akiyama, T., Tachibana, I., Shirohara, H., Watanabe, N., & Otsuki, M. (1996) · Diabetes Research and Clinical Practice · doi:10.1016/0168-8227(96)01205-3 · Cited by 183 · see citing works
Systems and WBANs for Controlling Obesity
Mohammed, M. S., Sendra, S., Lloret, J., & Reig, I. B. (2018) · Journal of Healthcare Engineering · doi:10.1155/2018/1564748 · Cited by 162 · see citing works
Hoehn, K. L., Turner, N., Swarbrick, M. M., Wilks, D., Preston, E., Phua, Y., Joshi, H., Furler, S. M., Larance, M., Hegarty, B. D., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2009.11.008 · Cited by 156 · see citing works
Feng, Y., Yu, Y., Wang, S.-T., Ren, J., Camer, D., Hua, Y.-Z., Zhang, Q. Y., Huang, J., Xue, D., Zhang, X.-F., et al. (2016) · Pharmaceutical Biology · doi:10.3109/13880209.2015.1093510 · Cited by 137 · see citing works
Treating the metabolic syndrome: acetyl-CoA carboxylase inhibition
Harwood, H. J., Jr. (2005) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.9.2.267 · Cited by 127 · see citing works
Gene knockout of Acc2 has little effect on body weight, fat mass, or food intake
Olson, D. P., Pulinilkunnil, T., Cline, G. W., Shulman, G. I., & Lowell, B. B. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913492107 · Cited by 109 · see citing works
Kim, C.-W., Addy, C., Kusunoki, J., Anderson, N. N., Deja, S., Fu, X., Burgess, S. C., Cai, L., Ruddy, M., Chakravarthy, M. V., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.011 · Cited by 105 · see citing works
Role of malonyl-CoA in heart disease and the hypothalamic control of obesity
Folmes, C. D. L., & LOPASCHUK, G. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.10.008 · Cited by 95 · see citing works
The malonyl CoA axis as a potential target for treating ischaemic heart disease
Ussher, J. R., & Lopaschuk, G. D. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn130 · Cited by 94 · see citing works
Gou, L., Zhao, L., Song, W., Wang, L., Liu, J., Zhang, H., Huang, Y., Lau, C. W., Yao, X., Tian, X. Y., et al. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7005 · Cited by 86 · see citing works
Self-citationFatty Acid Metabolism, the Central Nervous System, and Feeding
Ronnett, G. V., Kleman, A. M., Kim, E. K., Landree, L. E., & Tu, Y. (2006) · Obesity · doi:10.1038/oby.2006.309 · Cited by 81 · see citing works
Protective effect of erythropoietin in neonatal hypoxic ischemia in mice
Matsushita, H., Johnston, M. V., Lange, M. S., & Wilson, M. A. (2003) · Neuroreport · doi:10.1097/00001756-200309150-00020 · Cited by 76 · see citing works
Fatty acid metabolism in cardiac failure: biochemical, genetic and cellular analysis
Marı́n-Garcı́a, J. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(01)00552-1 · Cited by 61 · see citing works
Lu, J., Jing, J., Yao, Q., Fan, K., Wang, G., Feng, R.-X., Liang, Y., Chen, L., Ge, Y., & Yao, B. (2016) · PLoS ONE · doi:10.1371/journal.pone.0146304 · Cited by 57 · see citing works
Eleftheriadis, T., Pissas, G., Antoniadi, G., Liakopoulos, V., & Stefanidis, I. (2015) · Immunology · doi:10.1111/imm.12502 · Cited by 56 · see citing works
Malonyl-CoA decarboxylase is a major regulator of myocardial fatty acid oxidation
Cuthbert, K. D., & Dyck, J. R. B. (2005) · Current Hypertension Reports · doi:10.1007/s11906-005-0034-z · Cited by 44 · see citing works
Dominiczak, M. H. (2003) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2003.194 · Cited by 37 · see citing works
Glund, S., Schoelch, C., Thomas, L. H., Niessen, H. G., Stiller, D., Roth, G. J., & Neubauer, H. (2012) · Diabetologia · doi:10.1007/s00125-012-2554-9 · Cited by 35 · see citing works
The Role of Fatty Acid Oxidation in the Metabolic Reprograming of Activated T-Cells
Byersdorfer, C. A. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00641 · Cited by 32 · see citing works
Eleftheriadis, T., Pissas, G., Liakopoulos, V., & Stefanidis, I. (2018) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2018.3624 · Cited by 29 · see citing works
Huang, T., Sun, J., Wang, Q., Gao, J., & Liu, Y. (2015) · Molecules · doi:10.3390/molecules200916221 · Cited by 27 · see citing works
Self-citationEleftheriadis, T., Pissas, G., Sounidaki, M., Tsogka, K., Antoniadis, N., Antoniadi, G., Liakopoulos, V., & Stefanidis, I. (2016) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2016.2750 · Cited by 27 · see citing works
Tetramethylpyrazine reduces inflammation in the livers of mice fed a high fat diet
Chen, B., Ma, Y., Xue, X., Wei, J., Hu, G., & Lin, Y. (2019) · Molecular Medicine Reports · doi:10.3892/mmr.2019.9928 · Cited by 15 · see citing works
Eleftheriadis, T., Pissas, G., Sounidaki, M., Antoniadi, G., Rountas, C., Liakopoulos, V., & Stefanidis, L. (2016) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-016-2915-7 · Cited by 8 · see citing works
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Batchuluun, B., Pinkosky, S. L., & Steinberg, G. R. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00367-2 · Cited by 402 · see citing works
Benzimidazoles in Drug Discovery: A Patent Review
Law, C. S. W., & Yeong, K. Y. (2021) · ChemMedChem · doi:10.1002/cmdc.202100004 · Cited by 93 · see citing works
A Patent Review on the Current Developments of Benzoxazoles in Drug Discovery
Wong, X. K., & Yeong, K. Y. (2021) · ChemMedChem · doi:10.1002/cmdc.202100370 · Cited by 84 · see citing works
Naomi, R., Bahari, H., Yazid, M. D., Othman, F., Zakaria, Z. A., & Hussain, M. K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910816 · Cited by 30 · see citing works
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Xu, Z., Liu, D., Liu, D., Ren, X., Liu, H., Qi, G., Zhou, Y. T., Wu, C., Zhu, K., Zou, Z., et al. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.01.006 · Cited by 28 · see citing works
Synthesis and Pharmacological Properties of the Benzimidazole Scaffold: A Patent Review
Mehra, A., & Sangwan, R. (2023) · ChemistrySelect · doi:10.1002/slct.202300537 · Cited by 13 · see citing works
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Wan, Q., Calhoun, C., Zahr, T., & Qiang, L. (2023) · Biomedicines · doi:10.3390/biomedicines11041132 · Cited by 10 · see citing works
Ali, I., Khan, A., Fa, Z., Khan, T., Wei, D., & Zheng, J. (2022) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2022.105439 · Cited by 9 · see citing works
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- Authors
- Liu, T., Gou, L., Yan, S., & Huang, T.
- Affiliations
- Department of Pharmacy, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China
- Xuzhou Medical College (CN)
- Corresponding author
- Huang, Tonghui
- Venue
- Experimental and Therapeutic Medicine
- Publisher
- Spandidos Publications
- Published
- 2020-04-29
- Volume
- 20
- Issue
- 1
- Pages
- 521-529
- ISSN
- 1792-0981 (ISSN-L)
- 1792-1015
- PMC
- PMC7296295
- OpenAlex
- W3022156204
- Cited by
- 15
- References
- 51
- Citations by year
- 2026: 2 · 2025: 3 · 2023: 3 · 2022: 4 · 2021: 3
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Experimental and Therapeutic Medicine (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81703493)
- China Postdoctoral Science Foundation (2019M661943, 2017M611916)
- Government of Jiangsu Province
- Natural Science Foundation of Jiangsu Province (BK20170258, BK20171184)
- Jiangsu Planned Projects for Postdoctoral Research Funds (1701132C)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- acetyl-CoA carboxylase inhibition, diet-induced obesity, high-fat diet, malonyl-CoA, impaired glucose tolerance, hepatic lipid accumulation, serum triglycerides, free fatty acids, fatty acid metabolism, structure-based drug design
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