High expression of P4HA3 in obesity: a potential therapeutic target for type 2 diabetes
The aims of the present study were to evaluate the expression of prolyl 4-hydroxylase subunit alpha 3 (P4HA3) in adipocytes and adipose tissue and to explore its effect on obesity and type 2 diabetes mellitus (T2DM). We initially demonstrated that P4HA3 was significantly upregulated in the subcutane...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
2022-08-01
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| Series: | Brazilian Journal of Medical and Biological Research |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2022000100652&tlng=en |
| _version_ | 1811215178687053824 |
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| author | Langen Zhuang Can Li Xiaolei Hu Qingqing Yang Xiaoyan Pei Guoxi Jin |
| author_facet | Langen Zhuang Can Li Xiaolei Hu Qingqing Yang Xiaoyan Pei Guoxi Jin |
| author_sort | Langen Zhuang |
| collection | DOAJ |
| description | The aims of the present study were to evaluate the expression of prolyl 4-hydroxylase subunit alpha 3 (P4HA3) in adipocytes and adipose tissue and to explore its effect on obesity and type 2 diabetes mellitus (T2DM). We initially demonstrated that P4HA3 was significantly upregulated in the subcutaneous adipose tissue of obesity and T2DM patients, and its functional roles in adipocyte differentiation and insulin resistance were investigated using in vitro and in vivo models. The knockdown of P4HA3 inhibited adipocyte differentiation and improved insulin resistance in 3T3-L1 cells. In C57BL/6J db/db mice fed with a high fat diet (HFD), silencing P4HA3 significantly decreased fasting blood glucose and triglycerides (TG) levels, with concomitant decrease of body weight and adipose tissue weight. Further analysis showed that P4HA3 knockdown was correlated with the augmented IRS-1/PI3K/Akt/FoxO1 signaling pathway in the adipose and hepatic tissues of obese mice, which could improve hepatic glucose homeostasis and steatosis of mice. Together, our study suggested that the dysregulation of P4HA3 may contribute to the development of obesity and T2DM. |
| first_indexed | 2024-04-12T06:17:45Z |
| format | Article |
| id | doaj.art-089873760f244045809df61efbba6aef |
| institution | Directory Open Access Journal |
| issn | 1414-431X |
| language | English |
| last_indexed | 2024-04-12T06:17:45Z |
| publishDate | 2022-08-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-089873760f244045809df61efbba6aef2022-12-22T03:44:24ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X2022-08-015510.1590/1414-431x2022e11741High expression of P4HA3 in obesity: a potential therapeutic target for type 2 diabetesLangen Zhuanghttps://orcid.org/0000-0003-3700-2715Can Lihttps://orcid.org/0000-0002-9749-5016Xiaolei Huhttps://orcid.org/0000-0001-7536-603XQingqing Yanghttps://orcid.org/0000-0001-6214-3750Xiaoyan Peihttps://orcid.org/0000-0001-5404-8614Guoxi Jinhttps://orcid.org/0000-0001-5944-9142The aims of the present study were to evaluate the expression of prolyl 4-hydroxylase subunit alpha 3 (P4HA3) in adipocytes and adipose tissue and to explore its effect on obesity and type 2 diabetes mellitus (T2DM). We initially demonstrated that P4HA3 was significantly upregulated in the subcutaneous adipose tissue of obesity and T2DM patients, and its functional roles in adipocyte differentiation and insulin resistance were investigated using in vitro and in vivo models. The knockdown of P4HA3 inhibited adipocyte differentiation and improved insulin resistance in 3T3-L1 cells. In C57BL/6J db/db mice fed with a high fat diet (HFD), silencing P4HA3 significantly decreased fasting blood glucose and triglycerides (TG) levels, with concomitant decrease of body weight and adipose tissue weight. Further analysis showed that P4HA3 knockdown was correlated with the augmented IRS-1/PI3K/Akt/FoxO1 signaling pathway in the adipose and hepatic tissues of obese mice, which could improve hepatic glucose homeostasis and steatosis of mice. Together, our study suggested that the dysregulation of P4HA3 may contribute to the development of obesity and T2DM.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2022000100652&tlng=enP4HA3ObesityT2DM |
| spellingShingle | Langen Zhuang Can Li Xiaolei Hu Qingqing Yang Xiaoyan Pei Guoxi Jin High expression of P4HA3 in obesity: a potential therapeutic target for type 2 diabetes Brazilian Journal of Medical and Biological Research P4HA3 Obesity T2DM |
| title | High expression of P4HA3 in obesity: a potential therapeutic target for type 2 diabetes |
| title_full | High expression of P4HA3 in obesity: a potential therapeutic target for type 2 diabetes |
| title_fullStr | High expression of P4HA3 in obesity: a potential therapeutic target for type 2 diabetes |
| title_full_unstemmed | High expression of P4HA3 in obesity: a potential therapeutic target for type 2 diabetes |
| title_short | High expression of P4HA3 in obesity: a potential therapeutic target for type 2 diabetes |
| title_sort | high expression of p4ha3 in obesity a potential therapeutic target for type 2 diabetes |
| topic | P4HA3 Obesity T2DM |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2022000100652&tlng=en |
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