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The Effects of New Selective PPARα Agonist CP775146 on Systematic Lipid Metabolism in Obese Mice and Its Potential Mechanism
PURPOSE: Peroxisome proliferator-activated receptor α (PPARα) plays a crucial role in the control of lipid homeostasis. Here, we investigated the effects of CP775146, a new selective PPARα agonist, on lipid metabolism in diet-induced obese mice and its possible mechanism. METHODS: C57BL/6 mice were...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222497/ https://www.ncbi.nlm.nih.gov/pubmed/32455134 http://dx.doi.org/10.1155/2020/4179852 |
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author | Tang, Shengjie Wu, Fang Lin, Xihua Gui, Weiwei Zheng, Fenping Li, Hong |
author_facet | Tang, Shengjie Wu, Fang Lin, Xihua Gui, Weiwei Zheng, Fenping Li, Hong |
author_sort | Tang, Shengjie |
collection | PubMed |
description | PURPOSE: Peroxisome proliferator-activated receptor α (PPARα) plays a crucial role in the control of lipid homeostasis. Here, we investigated the effects of CP775146, a new selective PPARα agonist, on lipid metabolism in diet-induced obese mice and its possible mechanism. METHODS: C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity and then received CP775146 via intraperitoneal injection for 3 days. The content/morphology of the liver, serum lipid, and liver function was measured. The expression of genes related to lipolysis and synthesis in liver was detected by quantitative real-time PCR (qRT-PCR). RESULTS: The safe dose of CP775146 was <0.3 mg/kg. CP775146 reduced the serum levels of liver enzymes, such as alanine aminotransferase (ALT) and glutamic-oxaloacetic transaminase (AST) and lipid metabolism-related biomarkers, including triglycerides (TGs) and low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein cholesterol (non-HDL-c), and hepatic TG content, at a dosage of 0.1 mg/kg. HFD-induced pathological liver changes improved after CP775146 treatment. The expression of genes involved in liver fatty acid oxidation (acyl-coenzyme A dehydrogenase, long chain (Acadl), acyl-CoA oxidase 1 (Acox-1), carnitine palmitoyltransferase-1 (CPT-1), and enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase (Ehhadh)) was upregulated in CP775146-treated mice. Furthermore, CP775146 induced the expression of thermogenesis genes (cell death-inducing DFFA-like effector a (Cidea), uncoupling protein 1 (Ucp1)) and lipolysis genes (hormone-sensitive lipase (Hsl), adipose tissue triglyceride lipase (Atgl)) in epididymal white adipose tissue (eWAT), activating browning and thermogenesis. CONCLUSION: CP775146 efficiently alleviates obesity-induced liver damage, prevents lipid accumulation by activating the liver fatty acid β-oxidation pathway, and regulates the expression of genes that control brown fat-like pathway in eWAT. |
format | Online Article Text |
id | pubmed-7222497 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-72224972020-05-23 The Effects of New Selective PPARα Agonist CP775146 on Systematic Lipid Metabolism in Obese Mice and Its Potential Mechanism Tang, Shengjie Wu, Fang Lin, Xihua Gui, Weiwei Zheng, Fenping Li, Hong J Diabetes Res Research Article PURPOSE: Peroxisome proliferator-activated receptor α (PPARα) plays a crucial role in the control of lipid homeostasis. Here, we investigated the effects of CP775146, a new selective PPARα agonist, on lipid metabolism in diet-induced obese mice and its possible mechanism. METHODS: C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity and then received CP775146 via intraperitoneal injection for 3 days. The content/morphology of the liver, serum lipid, and liver function was measured. The expression of genes related to lipolysis and synthesis in liver was detected by quantitative real-time PCR (qRT-PCR). RESULTS: The safe dose of CP775146 was <0.3 mg/kg. CP775146 reduced the serum levels of liver enzymes, such as alanine aminotransferase (ALT) and glutamic-oxaloacetic transaminase (AST) and lipid metabolism-related biomarkers, including triglycerides (TGs) and low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein cholesterol (non-HDL-c), and hepatic TG content, at a dosage of 0.1 mg/kg. HFD-induced pathological liver changes improved after CP775146 treatment. The expression of genes involved in liver fatty acid oxidation (acyl-coenzyme A dehydrogenase, long chain (Acadl), acyl-CoA oxidase 1 (Acox-1), carnitine palmitoyltransferase-1 (CPT-1), and enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase (Ehhadh)) was upregulated in CP775146-treated mice. Furthermore, CP775146 induced the expression of thermogenesis genes (cell death-inducing DFFA-like effector a (Cidea), uncoupling protein 1 (Ucp1)) and lipolysis genes (hormone-sensitive lipase (Hsl), adipose tissue triglyceride lipase (Atgl)) in epididymal white adipose tissue (eWAT), activating browning and thermogenesis. CONCLUSION: CP775146 efficiently alleviates obesity-induced liver damage, prevents lipid accumulation by activating the liver fatty acid β-oxidation pathway, and regulates the expression of genes that control brown fat-like pathway in eWAT. Hindawi 2020-05-04 /pmc/articles/PMC7222497/ /pubmed/32455134 http://dx.doi.org/10.1155/2020/4179852 Text en Copyright © 2020 Shengjie Tang et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Tang, Shengjie Wu, Fang Lin, Xihua Gui, Weiwei Zheng, Fenping Li, Hong The Effects of New Selective PPARα Agonist CP775146 on Systematic Lipid Metabolism in Obese Mice and Its Potential Mechanism |
title | The Effects of New Selective PPARα Agonist CP775146 on Systematic Lipid Metabolism in Obese Mice and Its Potential Mechanism |
title_full | The Effects of New Selective PPARα Agonist CP775146 on Systematic Lipid Metabolism in Obese Mice and Its Potential Mechanism |
title_fullStr | The Effects of New Selective PPARα Agonist CP775146 on Systematic Lipid Metabolism in Obese Mice and Its Potential Mechanism |
title_full_unstemmed | The Effects of New Selective PPARα Agonist CP775146 on Systematic Lipid Metabolism in Obese Mice and Its Potential Mechanism |
title_short | The Effects of New Selective PPARα Agonist CP775146 on Systematic Lipid Metabolism in Obese Mice and Its Potential Mechanism |
title_sort | effects of new selective pparα agonist cp775146 on systematic lipid metabolism in obese mice and its potential mechanism |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222497/ https://www.ncbi.nlm.nih.gov/pubmed/32455134 http://dx.doi.org/10.1155/2020/4179852 |
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