Liver-specific overexpression of lipoprotein lipase improves glucose metabolism in high-fat diet-fed mice.
The liver is the main organ that regulates lipid and glucose metabolism. Ectopic lipid accumulation in the liver impairs insulin sensitivity and glucose metabolism. Lipoprotein lipase (LPL), mainly expressed in the adipose tissue and muscle, is a key enzyme that regulates lipid metabolism via the hy...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0274297 |
| _version_ | 1818030255867166720 |
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| author | Kahori Shimizu Syogo Nishimuta Yuri Fukumura Shotaro Michinaga Yuka Egusa Tomomi Hase Tomoyuki Terada Fuminori Sakurai Hiroyuki Mizuguchi Koji Tomita Toru Nishinaka |
| author_facet | Kahori Shimizu Syogo Nishimuta Yuri Fukumura Shotaro Michinaga Yuka Egusa Tomomi Hase Tomoyuki Terada Fuminori Sakurai Hiroyuki Mizuguchi Koji Tomita Toru Nishinaka |
| author_sort | Kahori Shimizu |
| collection | DOAJ |
| description | The liver is the main organ that regulates lipid and glucose metabolism. Ectopic lipid accumulation in the liver impairs insulin sensitivity and glucose metabolism. Lipoprotein lipase (LPL), mainly expressed in the adipose tissue and muscle, is a key enzyme that regulates lipid metabolism via the hydrolysis of triglyceride in chylomicrons and very-low-density lipoproteins. Here, we aimed to investigate whether the suppression level of hepatic lipid accumulation via overexpression of LPL in mouse liver leads to improved metabolism. To overexpress LPL in the liver, we generated an LPL-expressing adenovirus (Ad) vector using an improved Ad vector that exhibited considerably lower hepatotoxicity (Ad-LPL). C57BL/6 mice were treated with Ad vectors and simultaneously fed a high-fat diet (HFD). Lipid droplet formation in the liver decreased in Ad-LPL-treated mice relative to that in control Ad vector-treated mice. Glucose tolerance and insulin resistance were remarkably improved in Ad-LPL-treated mice compared to those in control Ad vector-treated mice. The expression levels of fatty acid oxidation-related genes, such as peroxisome proliferator-activated receptor α, carnitine palmitoyltransferase 1, and acyl-CoA oxidase 1, were 1.7-2.0-fold higher in Ad-LPL-treated mouse livers than that in control Ad-vector-treated mouse livers. Furthermore, hepatic LPL overexpression partly maintained mitochondrial content in HFD-fed mice. These results indicate that LPL overexpression in the livers of HFD-fed mice attenuates the accumulation of lipid droplets in the liver and improves glucose metabolism. These findings may enable the development of new drugs to treat metabolic syndromes such as type 2 diabetes mellitus and non-alcoholic fatty liver disease. |
| first_indexed | 2024-12-10T05:32:41Z |
| format | Article |
| id | doaj.art-43b57908284e46f9960d1a8ccb6ca095 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T05:32:41Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-43b57908284e46f9960d1a8ccb6ca0952022-12-22T02:00:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01179e027429710.1371/journal.pone.0274297Liver-specific overexpression of lipoprotein lipase improves glucose metabolism in high-fat diet-fed mice.Kahori ShimizuSyogo NishimutaYuri FukumuraShotaro MichinagaYuka EgusaTomomi HaseTomoyuki TeradaFuminori SakuraiHiroyuki MizuguchiKoji TomitaToru NishinakaThe liver is the main organ that regulates lipid and glucose metabolism. Ectopic lipid accumulation in the liver impairs insulin sensitivity and glucose metabolism. Lipoprotein lipase (LPL), mainly expressed in the adipose tissue and muscle, is a key enzyme that regulates lipid metabolism via the hydrolysis of triglyceride in chylomicrons and very-low-density lipoproteins. Here, we aimed to investigate whether the suppression level of hepatic lipid accumulation via overexpression of LPL in mouse liver leads to improved metabolism. To overexpress LPL in the liver, we generated an LPL-expressing adenovirus (Ad) vector using an improved Ad vector that exhibited considerably lower hepatotoxicity (Ad-LPL). C57BL/6 mice were treated with Ad vectors and simultaneously fed a high-fat diet (HFD). Lipid droplet formation in the liver decreased in Ad-LPL-treated mice relative to that in control Ad vector-treated mice. Glucose tolerance and insulin resistance were remarkably improved in Ad-LPL-treated mice compared to those in control Ad vector-treated mice. The expression levels of fatty acid oxidation-related genes, such as peroxisome proliferator-activated receptor α, carnitine palmitoyltransferase 1, and acyl-CoA oxidase 1, were 1.7-2.0-fold higher in Ad-LPL-treated mouse livers than that in control Ad-vector-treated mouse livers. Furthermore, hepatic LPL overexpression partly maintained mitochondrial content in HFD-fed mice. These results indicate that LPL overexpression in the livers of HFD-fed mice attenuates the accumulation of lipid droplets in the liver and improves glucose metabolism. These findings may enable the development of new drugs to treat metabolic syndromes such as type 2 diabetes mellitus and non-alcoholic fatty liver disease.https://doi.org/10.1371/journal.pone.0274297 |
| spellingShingle | Kahori Shimizu Syogo Nishimuta Yuri Fukumura Shotaro Michinaga Yuka Egusa Tomomi Hase Tomoyuki Terada Fuminori Sakurai Hiroyuki Mizuguchi Koji Tomita Toru Nishinaka Liver-specific overexpression of lipoprotein lipase improves glucose metabolism in high-fat diet-fed mice. PLoS ONE |
| title | Liver-specific overexpression of lipoprotein lipase improves glucose metabolism in high-fat diet-fed mice. |
| title_full | Liver-specific overexpression of lipoprotein lipase improves glucose metabolism in high-fat diet-fed mice. |
| title_fullStr | Liver-specific overexpression of lipoprotein lipase improves glucose metabolism in high-fat diet-fed mice. |
| title_full_unstemmed | Liver-specific overexpression of lipoprotein lipase improves glucose metabolism in high-fat diet-fed mice. |
| title_short | Liver-specific overexpression of lipoprotein lipase improves glucose metabolism in high-fat diet-fed mice. |
| title_sort | liver specific overexpression of lipoprotein lipase improves glucose metabolism in high fat diet fed mice |
| url | https://doi.org/10.1371/journal.pone.0274297 |
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