Upregulation of hypothalamic POMC neurons after biliary diversion in GK rats
BackgroundBile acids are important signaling molecules that might activate hypothalamic neurons. This study aimed to investigate possible changes in hypothalamic pro-opiomelanocortin (POMC) neurons after biliary diversion in diabetic rats.MethodsTen GK rats were randomly divided into the biliary div...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-10-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.999928/full |
| _version_ | 1797996486311542784 |
|---|---|
| author | Shengnan Zhou Weijie Chen Xuesong Bai Jiemin Chen Qiang Xu Liangbo Dong Wei Chen Qiang Qu Xiaodong He |
| author_facet | Shengnan Zhou Weijie Chen Xuesong Bai Jiemin Chen Qiang Xu Liangbo Dong Wei Chen Qiang Qu Xiaodong He |
| author_sort | Shengnan Zhou |
| collection | DOAJ |
| description | BackgroundBile acids are important signaling molecules that might activate hypothalamic neurons. This study aimed to investigate possible changes in hypothalamic pro-opiomelanocortin (POMC) neurons after biliary diversion in diabetic rats.MethodsTen GK rats were randomly divided into the biliary diversion (BD) and sham groups. The glucose metabolism, hypothalamic POMC expression, serum bile acid profiles, and ileal bile acid-specific receptors of the two groups were analyzed.ResultsBiliary diversion improved blood glucose (P = 0.001) and glucose tolerance (P = 0.001). RNA-Seq of the hypothalamus showed significantly upregulated expression of the POMC gene (log2-fold change = 4.1, P < 0.001), which also showed increased expression at the protein (P = 0.030) and mRNA (P = 0.004) levels. The POMC-derived neuropeptide α-melanocyte stimulating hormone (α-MSH) was also increased in the hypothalamus (2.21 ± 0.11 ng/g, P = 0.006). In addition, increased taurocholic acid (TCA) (108.05 ± 20.62 ng/mL, P = 0.003) and taurodeoxycholic acid (TDCA) (45.58 ± 2.74 ng/mL, P < 0.001) were found in the BD group and induced the enhanced secretion of fibroblast growth factor-15 (FGF15, 74.28 ± 3.44 pg/ml, P = 0.001) by activating farnesoid X receptor (FXR) that was over-expressed in the ileum.ConclusionsHypothalamic POMC neurons were upregulated after BD, and the increased TCA, TDCA, and the downstream gut-derived hormone FGF15 might activate POMC neurons. |
| first_indexed | 2024-04-11T10:18:09Z |
| format | Article |
| id | doaj.art-512f151b36e946dc83d6de2e29505610 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-11T10:18:09Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-512f151b36e946dc83d6de2e295056102022-12-22T04:29:51ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-10-011310.3389/fendo.2022.999928999928Upregulation of hypothalamic POMC neurons after biliary diversion in GK ratsShengnan Zhou0Weijie Chen1Xuesong Bai2Jiemin Chen3Qiang Xu4Liangbo Dong5Wei Chen6Qiang Qu7Xiaodong He8Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, ChinaDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, ChinaDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, ChinaGastroenterology Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, ChinaDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, ChinaDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, ChinaClinical Nutrition Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, ChinaDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, ChinaDepartment of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, ChinaBackgroundBile acids are important signaling molecules that might activate hypothalamic neurons. This study aimed to investigate possible changes in hypothalamic pro-opiomelanocortin (POMC) neurons after biliary diversion in diabetic rats.MethodsTen GK rats were randomly divided into the biliary diversion (BD) and sham groups. The glucose metabolism, hypothalamic POMC expression, serum bile acid profiles, and ileal bile acid-specific receptors of the two groups were analyzed.ResultsBiliary diversion improved blood glucose (P = 0.001) and glucose tolerance (P = 0.001). RNA-Seq of the hypothalamus showed significantly upregulated expression of the POMC gene (log2-fold change = 4.1, P < 0.001), which also showed increased expression at the protein (P = 0.030) and mRNA (P = 0.004) levels. The POMC-derived neuropeptide α-melanocyte stimulating hormone (α-MSH) was also increased in the hypothalamus (2.21 ± 0.11 ng/g, P = 0.006). In addition, increased taurocholic acid (TCA) (108.05 ± 20.62 ng/mL, P = 0.003) and taurodeoxycholic acid (TDCA) (45.58 ± 2.74 ng/mL, P < 0.001) were found in the BD group and induced the enhanced secretion of fibroblast growth factor-15 (FGF15, 74.28 ± 3.44 pg/ml, P = 0.001) by activating farnesoid X receptor (FXR) that was over-expressed in the ileum.ConclusionsHypothalamic POMC neurons were upregulated after BD, and the increased TCA, TDCA, and the downstream gut-derived hormone FGF15 might activate POMC neurons.https://www.frontiersin.org/articles/10.3389/fendo.2022.999928/fullbiliary diversionbile acidsFGF15POMC neuronsmetabolism |
| spellingShingle | Shengnan Zhou Weijie Chen Xuesong Bai Jiemin Chen Qiang Xu Liangbo Dong Wei Chen Qiang Qu Xiaodong He Upregulation of hypothalamic POMC neurons after biliary diversion in GK rats Frontiers in Endocrinology biliary diversion bile acids FGF15 POMC neurons metabolism |
| title | Upregulation of hypothalamic POMC neurons after biliary diversion in GK rats |
| title_full | Upregulation of hypothalamic POMC neurons after biliary diversion in GK rats |
| title_fullStr | Upregulation of hypothalamic POMC neurons after biliary diversion in GK rats |
| title_full_unstemmed | Upregulation of hypothalamic POMC neurons after biliary diversion in GK rats |
| title_short | Upregulation of hypothalamic POMC neurons after biliary diversion in GK rats |
| title_sort | upregulation of hypothalamic pomc neurons after biliary diversion in gk rats |
| topic | biliary diversion bile acids FGF15 POMC neurons metabolism |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.999928/full |
| work_keys_str_mv | AT shengnanzhou upregulationofhypothalamicpomcneuronsafterbiliarydiversioningkrats AT weijiechen upregulationofhypothalamicpomcneuronsafterbiliarydiversioningkrats AT xuesongbai upregulationofhypothalamicpomcneuronsafterbiliarydiversioningkrats AT jieminchen upregulationofhypothalamicpomcneuronsafterbiliarydiversioningkrats AT qiangxu upregulationofhypothalamicpomcneuronsafterbiliarydiversioningkrats AT liangbodong upregulationofhypothalamicpomcneuronsafterbiliarydiversioningkrats AT weichen upregulationofhypothalamicpomcneuronsafterbiliarydiversioningkrats AT qiangqu upregulationofhypothalamicpomcneuronsafterbiliarydiversioningkrats AT xiaodonghe upregulationofhypothalamicpomcneuronsafterbiliarydiversioningkrats |