Exendin-4 Improves Diabetic Kidney Disease in C57BL/6 Mice Independent of Brown Adipose Tissue Activation
Background. The role of exendin-4 in brown adipose tissue (BAT) activation was not very clear. This study is to verify the role of BAT involved in renal benefits of exendin-4 in diabetes mellitus (DM). Methods. In vivo, C57BL/6 mice were randomly divided into nondiabetic (control) and diabetic group...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2020/9084567 |
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| author | Shu Fang Yingying Cai Fuping Lyu Hongbin Zhang Chunyan Wu Yanmei Zeng Cunxia Fan Shaozhou Zou Yudan Zhang Ping Li Ling Wang YaomingXue Meiping Guan |
| author_facet | Shu Fang Yingying Cai Fuping Lyu Hongbin Zhang Chunyan Wu Yanmei Zeng Cunxia Fan Shaozhou Zou Yudan Zhang Ping Li Ling Wang YaomingXue Meiping Guan |
| author_sort | Shu Fang |
| collection | DOAJ |
| description | Background. The role of exendin-4 in brown adipose tissue (BAT) activation was not very clear. This study is to verify the role of BAT involved in renal benefits of exendin-4 in diabetes mellitus (DM). Methods. In vivo, C57BL/6 mice were randomly divided into nondiabetic (control) and diabetic groups (DM). The diabetic mice were randomized into a control group (DM-Con), BAT-excision group (DM+Exc), exendin-4-treated group (DM+E4), and BAT-excision plus exendin-4-treated group (DM+Exc+E4). The weight, blood glucose and lipids, 24 h urine albumin and 8-OH-dG, and renal fibrosis were analyzed. In vitro, we investigated the role of exendin-4 in the differentiation process of 3T3-L1 and brown preadipocytes and its effect on the rat mesangial cells induced by oleate. Results. The expressions of UCP-1, PGC-1α, ATGL, and CD36 in BAT of DM mice were all downregulated, which could be upregulated by exendin-4 treatment with significant effects on ATGL and CD36. BAT-excision exacerbated high blood glucose (BG) with no significant effect on the serum lipid level. Exendin-4 significantly lowered the level of serum triglycerides (TG) and low-density lipoprotein- (LDL-) c, 24 h urine albumin, and 8-OH-dG; improved renal fibrosis and lipid accumulation; and activated renal AMP-activated protein kinase (AMPK) in diabetic mice regardless of BAT excision. In vitro, there was no significant effect of exendin-4 on brown or white adipogenesis. However, exendin-4 could improve lipid accumulation and myofibroblast-like phenotype transition of mesangial cells induced by oleate via activating the AMPK pathway. Conclusions. Exendin-4 could decrease the renal lipid deposit and improve diabetic nephropathy via activating the renal AMPK pathway independent of BAT activation. |
| format | Article |
| id | doaj-art-e156856ae8d14cc2aab4e7bf6f88336a |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-e156856ae8d14cc2aab4e7bf6f88336a2025-02-03T05:49:30ZengWileyJournal of Diabetes Research2314-67452314-67532020-01-01202010.1155/2020/90845679084567Exendin-4 Improves Diabetic Kidney Disease in C57BL/6 Mice Independent of Brown Adipose Tissue ActivationShu Fang0Yingying Cai1Fuping Lyu2Hongbin Zhang3Chunyan Wu4Yanmei Zeng5Cunxia Fan6Shaozhou Zou7Yudan Zhang8Ping Li9Ling Wang10YaomingXue11Meiping Guan12Department of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, ChinaDepartment of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, ChinaDepartment of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, ChinaDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, 2200, DenmarkDepartment of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, ChinaDepartment of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, ChinaDepartment of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, ChinaDepartment of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, ChinaDepartment of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, ChinaDepartment of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, ChinaDepartment of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, ChinaDepartment of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, ChinaDepartment of Endocrinology & Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, ChinaBackground. The role of exendin-4 in brown adipose tissue (BAT) activation was not very clear. This study is to verify the role of BAT involved in renal benefits of exendin-4 in diabetes mellitus (DM). Methods. In vivo, C57BL/6 mice were randomly divided into nondiabetic (control) and diabetic groups (DM). The diabetic mice were randomized into a control group (DM-Con), BAT-excision group (DM+Exc), exendin-4-treated group (DM+E4), and BAT-excision plus exendin-4-treated group (DM+Exc+E4). The weight, blood glucose and lipids, 24 h urine albumin and 8-OH-dG, and renal fibrosis were analyzed. In vitro, we investigated the role of exendin-4 in the differentiation process of 3T3-L1 and brown preadipocytes and its effect on the rat mesangial cells induced by oleate. Results. The expressions of UCP-1, PGC-1α, ATGL, and CD36 in BAT of DM mice were all downregulated, which could be upregulated by exendin-4 treatment with significant effects on ATGL and CD36. BAT-excision exacerbated high blood glucose (BG) with no significant effect on the serum lipid level. Exendin-4 significantly lowered the level of serum triglycerides (TG) and low-density lipoprotein- (LDL-) c, 24 h urine albumin, and 8-OH-dG; improved renal fibrosis and lipid accumulation; and activated renal AMP-activated protein kinase (AMPK) in diabetic mice regardless of BAT excision. In vitro, there was no significant effect of exendin-4 on brown or white adipogenesis. However, exendin-4 could improve lipid accumulation and myofibroblast-like phenotype transition of mesangial cells induced by oleate via activating the AMPK pathway. Conclusions. Exendin-4 could decrease the renal lipid deposit and improve diabetic nephropathy via activating the renal AMPK pathway independent of BAT activation.http://dx.doi.org/10.1155/2020/9084567 |
| spellingShingle | Shu Fang Yingying Cai Fuping Lyu Hongbin Zhang Chunyan Wu Yanmei Zeng Cunxia Fan Shaozhou Zou Yudan Zhang Ping Li Ling Wang YaomingXue Meiping Guan Exendin-4 Improves Diabetic Kidney Disease in C57BL/6 Mice Independent of Brown Adipose Tissue Activation Journal of Diabetes Research |
| title | Exendin-4 Improves Diabetic Kidney Disease in C57BL/6 Mice Independent of Brown Adipose Tissue Activation |
| title_full | Exendin-4 Improves Diabetic Kidney Disease in C57BL/6 Mice Independent of Brown Adipose Tissue Activation |
| title_fullStr | Exendin-4 Improves Diabetic Kidney Disease in C57BL/6 Mice Independent of Brown Adipose Tissue Activation |
| title_full_unstemmed | Exendin-4 Improves Diabetic Kidney Disease in C57BL/6 Mice Independent of Brown Adipose Tissue Activation |
| title_short | Exendin-4 Improves Diabetic Kidney Disease in C57BL/6 Mice Independent of Brown Adipose Tissue Activation |
| title_sort | exendin 4 improves diabetic kidney disease in c57bl 6 mice independent of brown adipose tissue activation |
| url | http://dx.doi.org/10.1155/2020/9084567 |
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