Osteocalcin Alleviates Nonalcoholic Fatty Liver Disease in Mice through GPRC6A
Osteocalcin is a bone-derived hormone that plays an important role in the crosstalk between bone and energy metabolism. Previous studies have found that treatment with uncarboxylated osteocalcin can protect mice from high-fat diet-induced nonalcoholic fatty liver disease (NAFLD). However, the potent...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2021/9178616 |
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| author | Mingliang Zhang Xiaomin Nie Yeqing Yuan Yansu Wang Xiaojing Ma Jun Yin Yuqian Bao |
| author_facet | Mingliang Zhang Xiaomin Nie Yeqing Yuan Yansu Wang Xiaojing Ma Jun Yin Yuqian Bao |
| author_sort | Mingliang Zhang |
| collection | DOAJ |
| description | Osteocalcin is a bone-derived hormone that plays an important role in the crosstalk between bone and energy metabolism. Previous studies have found that treatment with uncarboxylated osteocalcin can protect mice from high-fat diet-induced nonalcoholic fatty liver disease (NAFLD). However, the potential mechanisms remain unclear. Although the G protein-coupled receptor family C group 6 subtype A (GPRC6A) is the putative receptor of osteocalcin, there is no direct evidence showing that GPRC6A mediates the effects of uncarboxylated osteocalcin in alleviating NAFLD in mice. We aimed to figure out this using liver-specific GPRC6A knockout (GPRC6ALKO) mice. Consistent with previous studies, uncarboxylated osteocalcin significantly protected high-fat diet-fed wild-type mice from obesity and NAFLD, while it did not protect high-fat diet-fed GPRC6ALKO mice from NAFLD. Differential mRNA expression of lipogenesis and lipolysis between GPRC6ALKO mice and control mice revealed that GPRC6A mediated the effects of osteocalcin in alleviating NAFLD through inhibiting lipid synthesis and promoting lipolysis. In conclusion, this study found that uncarboxylated osteocalcin alleviates NAFLD in mice through the GPRC6A signaling pathway. Our study suggests that liver GPRC6A may be a potential target for treating NAFLD. |
| format | Article |
| id | doaj-art-b2f863924da548fca4f7a23023db80b5 |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-b2f863924da548fca4f7a23023db80b52025-02-03T01:04:20ZengWileyInternational Journal of Endocrinology1687-83371687-83452021-01-01202110.1155/2021/91786169178616Osteocalcin Alleviates Nonalcoholic Fatty Liver Disease in Mice through GPRC6AMingliang Zhang0Xiaomin Nie1Yeqing Yuan2Yansu Wang3Xiaojing Ma4Jun Yin5Yuqian Bao6Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai 200233, ChinaDepartment of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai 200233, ChinaDepartment of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai 200233, ChinaDepartment of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai 200233, ChinaDepartment of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai 200233, ChinaDepartment of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai 200233, ChinaDepartment of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai 200233, ChinaOsteocalcin is a bone-derived hormone that plays an important role in the crosstalk between bone and energy metabolism. Previous studies have found that treatment with uncarboxylated osteocalcin can protect mice from high-fat diet-induced nonalcoholic fatty liver disease (NAFLD). However, the potential mechanisms remain unclear. Although the G protein-coupled receptor family C group 6 subtype A (GPRC6A) is the putative receptor of osteocalcin, there is no direct evidence showing that GPRC6A mediates the effects of uncarboxylated osteocalcin in alleviating NAFLD in mice. We aimed to figure out this using liver-specific GPRC6A knockout (GPRC6ALKO) mice. Consistent with previous studies, uncarboxylated osteocalcin significantly protected high-fat diet-fed wild-type mice from obesity and NAFLD, while it did not protect high-fat diet-fed GPRC6ALKO mice from NAFLD. Differential mRNA expression of lipogenesis and lipolysis between GPRC6ALKO mice and control mice revealed that GPRC6A mediated the effects of osteocalcin in alleviating NAFLD through inhibiting lipid synthesis and promoting lipolysis. In conclusion, this study found that uncarboxylated osteocalcin alleviates NAFLD in mice through the GPRC6A signaling pathway. Our study suggests that liver GPRC6A may be a potential target for treating NAFLD.http://dx.doi.org/10.1155/2021/9178616 |
| spellingShingle | Mingliang Zhang Xiaomin Nie Yeqing Yuan Yansu Wang Xiaojing Ma Jun Yin Yuqian Bao Osteocalcin Alleviates Nonalcoholic Fatty Liver Disease in Mice through GPRC6A International Journal of Endocrinology |
| title | Osteocalcin Alleviates Nonalcoholic Fatty Liver Disease in Mice through GPRC6A |
| title_full | Osteocalcin Alleviates Nonalcoholic Fatty Liver Disease in Mice through GPRC6A |
| title_fullStr | Osteocalcin Alleviates Nonalcoholic Fatty Liver Disease in Mice through GPRC6A |
| title_full_unstemmed | Osteocalcin Alleviates Nonalcoholic Fatty Liver Disease in Mice through GPRC6A |
| title_short | Osteocalcin Alleviates Nonalcoholic Fatty Liver Disease in Mice through GPRC6A |
| title_sort | osteocalcin alleviates nonalcoholic fatty liver disease in mice through gprc6a |
| url | http://dx.doi.org/10.1155/2021/9178616 |
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