Depletion of Gut Microbiota Inhibits Hepatic Lipid Accumulation in High-Fat Diet-Fed Mice
Dysregulated lipid metabolism is a key pathology in metabolic diseases and the liver is a critical organ for lipid metabolism. The gut microbiota has been shown to regulate hepatic lipid metabolism in the host. However, the underlying mechanism by which the gut microbiota influences hepatic lipid me...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-08-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/16/9350 |
| _version_ | 1797444740733468672 |
|---|---|
| author | Hui Han Mengyu Wang Ruqing Zhong Bao Yi Martine Schroyen Hongfu Zhang |
| author_facet | Hui Han Mengyu Wang Ruqing Zhong Bao Yi Martine Schroyen Hongfu Zhang |
| author_sort | Hui Han |
| collection | DOAJ |
| description | Dysregulated lipid metabolism is a key pathology in metabolic diseases and the liver is a critical organ for lipid metabolism. The gut microbiota has been shown to regulate hepatic lipid metabolism in the host. However, the underlying mechanism by which the gut microbiota influences hepatic lipid metabolism has not been elucidated. Here, a gut microbiota depletion mouse model was constructed with an antibiotics cocktail (Abx) to study the mechanism through which intestinal microbiota regulates hepatic lipid metabolism in high-fat diet (HFD)-fed mice. Our results showed that the Abx treatment effectively eradicated the gut microbiota in these mice. Microbiota depletion reduced the body weight and fat deposition both in white adipose tissue and liver. In addition, microbiota depletion reduced serum levels of glucose, total cholesterol (TC), low-density lipoproteins (LDL), insulin, and leptin in HFD-fed mice. Importantly, the depletion of gut microbiota in HFD-fed mice inhibited excessive hepatic lipid accumulation. Mechanistically, RNA-seq results revealed that gut microbiota depletion changed the expression of hepatic genes involved in cholesterol and fatty acid metabolism, such as <i>Cd36</i>, <i>Mogat1</i>, <i>Cyp39a1</i>, <i>Abcc3</i>, and <i>Gpat3</i>. Moreover, gut microbiota depletion reduced the abundance of bacteria associated with abnormal metabolism and inflammation, including <i>Lachnospiraceae</i>, <i>Coriobacteriaceae_UCG-002</i>, <i>Enterorhabdus</i>, <i>Faecalibaculum</i>, and <i>Desulfovibrio</i>. Correlation analysis showed that there was strong association between the altered gut microbiota abundance and the serum cholesterol level. This study indicates that gut microbiota ameliorates HFD-induced hepatic lipid metabolic dysfunction, which might be associated with genes participating in cholesterol and fatty acid metabolism in the liver. |
| first_indexed | 2024-03-09T13:15:55Z |
| format | Article |
| id | doaj.art-dad5b712dc514999bd586d1411ed6024 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:15:55Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-dad5b712dc514999bd586d1411ed60242023-11-30T21:36:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316935010.3390/ijms23169350Depletion of Gut Microbiota Inhibits Hepatic Lipid Accumulation in High-Fat Diet-Fed MiceHui Han0Mengyu Wang1Ruqing Zhong2Bao Yi3Martine Schroyen4Hongfu Zhang5State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaState Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaState Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaState Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaPrecision Livestock and Nutrition Unit, Gembloux Agro-Bio Tech, University of Liège, 4000 Gembloux, BelgiumState Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaDysregulated lipid metabolism is a key pathology in metabolic diseases and the liver is a critical organ for lipid metabolism. The gut microbiota has been shown to regulate hepatic lipid metabolism in the host. However, the underlying mechanism by which the gut microbiota influences hepatic lipid metabolism has not been elucidated. Here, a gut microbiota depletion mouse model was constructed with an antibiotics cocktail (Abx) to study the mechanism through which intestinal microbiota regulates hepatic lipid metabolism in high-fat diet (HFD)-fed mice. Our results showed that the Abx treatment effectively eradicated the gut microbiota in these mice. Microbiota depletion reduced the body weight and fat deposition both in white adipose tissue and liver. In addition, microbiota depletion reduced serum levels of glucose, total cholesterol (TC), low-density lipoproteins (LDL), insulin, and leptin in HFD-fed mice. Importantly, the depletion of gut microbiota in HFD-fed mice inhibited excessive hepatic lipid accumulation. Mechanistically, RNA-seq results revealed that gut microbiota depletion changed the expression of hepatic genes involved in cholesterol and fatty acid metabolism, such as <i>Cd36</i>, <i>Mogat1</i>, <i>Cyp39a1</i>, <i>Abcc3</i>, and <i>Gpat3</i>. Moreover, gut microbiota depletion reduced the abundance of bacteria associated with abnormal metabolism and inflammation, including <i>Lachnospiraceae</i>, <i>Coriobacteriaceae_UCG-002</i>, <i>Enterorhabdus</i>, <i>Faecalibaculum</i>, and <i>Desulfovibrio</i>. Correlation analysis showed that there was strong association between the altered gut microbiota abundance and the serum cholesterol level. This study indicates that gut microbiota ameliorates HFD-induced hepatic lipid metabolic dysfunction, which might be associated with genes participating in cholesterol and fatty acid metabolism in the liver.https://www.mdpi.com/1422-0067/23/16/9350gut microbiotaliverlipid metabolismantibiotics cocktail (Abx)high-fat diet (HFD) |
| spellingShingle | Hui Han Mengyu Wang Ruqing Zhong Bao Yi Martine Schroyen Hongfu Zhang Depletion of Gut Microbiota Inhibits Hepatic Lipid Accumulation in High-Fat Diet-Fed Mice International Journal of Molecular Sciences gut microbiota liver lipid metabolism antibiotics cocktail (Abx) high-fat diet (HFD) |
| title | Depletion of Gut Microbiota Inhibits Hepatic Lipid Accumulation in High-Fat Diet-Fed Mice |
| title_full | Depletion of Gut Microbiota Inhibits Hepatic Lipid Accumulation in High-Fat Diet-Fed Mice |
| title_fullStr | Depletion of Gut Microbiota Inhibits Hepatic Lipid Accumulation in High-Fat Diet-Fed Mice |
| title_full_unstemmed | Depletion of Gut Microbiota Inhibits Hepatic Lipid Accumulation in High-Fat Diet-Fed Mice |
| title_short | Depletion of Gut Microbiota Inhibits Hepatic Lipid Accumulation in High-Fat Diet-Fed Mice |
| title_sort | depletion of gut microbiota inhibits hepatic lipid accumulation in high fat diet fed mice |
| topic | gut microbiota liver lipid metabolism antibiotics cocktail (Abx) high-fat diet (HFD) |
| url | https://www.mdpi.com/1422-0067/23/16/9350 |
| work_keys_str_mv | AT huihan depletionofgutmicrobiotainhibitshepaticlipidaccumulationinhighfatdietfedmice AT mengyuwang depletionofgutmicrobiotainhibitshepaticlipidaccumulationinhighfatdietfedmice AT ruqingzhong depletionofgutmicrobiotainhibitshepaticlipidaccumulationinhighfatdietfedmice AT baoyi depletionofgutmicrobiotainhibitshepaticlipidaccumulationinhighfatdietfedmice AT martineschroyen depletionofgutmicrobiotainhibitshepaticlipidaccumulationinhighfatdietfedmice AT hongfuzhang depletionofgutmicrobiotainhibitshepaticlipidaccumulationinhighfatdietfedmice |