Folate Deficiency Enhanced Inflammation and Exacerbated Renal Fibrosis in High-Fat High-Fructose Diet-Fed Mice
The prevalence of obesity and chronic kidney disease (CKD) is increasing simultaneously and rapidly worldwide. Our previous study showed that folate deficiency increased lipid accumulation and leptin production of adipocytes. Whether folate plays a role in CKD, particularly obesity-related nephropat...
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MDPI AG
2023-08-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/15/16/3616 |
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| author | Chun-Wai Chan Bi-Fong Lin |
| author_facet | Chun-Wai Chan Bi-Fong Lin |
| author_sort | Chun-Wai Chan |
| collection | DOAJ |
| description | The prevalence of obesity and chronic kidney disease (CKD) is increasing simultaneously and rapidly worldwide. Our previous study showed that folate deficiency increased lipid accumulation and leptin production of adipocytes. Whether folate plays a role in CKD, particularly obesity-related nephropathy remains unclear. To investigate the effects of folate deficiency on CKD in diet-induced obese mice, four groups of male C57BL/6 mice were fed either a normal-fat diet (NF) with folate (NF+f); NF without folate (NF−f); high-fat high-fructose diet (HFF) with folate (HFF+f); or HFF without folate (HFF−f) for 12 months during the study. The results showed that HFF increased not only body weight, fasting blood glucose, total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol, and blood pressure, but also cytokines levels, such as interleukin (IL)-2, interferon (IFN)-γ, IL-17A/F, IL-6, monocyte chemoattractant protein (MCP)-1, and transforming growth factor (TGF)-β1. The indicators of kidney failure including urinary protein, neutrophil gelatinase-associated lipocalin (NGAL), renal type I and IV collagen deposits and leptin content, and serum creatinine were also increased by HFF. Folate-deficient diets further elevated serum TC, LDL-cholesterol, IL-6, tumor necrosis factor (TNF)-α, MCP-1, TGF-β1, and leptin, but decreased IL-10 level, and thus exacerbated renal fibrosis. To investigate the possible mechanisms of folate deficiency on renal injury, phosphorylation of pro-fibrosis signaling molecules, including signal transducer and activator of transcription (STAT)3 and small mothers against decapentaplegic (Smad)2/3, were assayed. Both HFF and folate deficiency significantly increased the phosphorylation of STAT3 and Smad2/3, suggesting synergistic effects of HFF−f on chronic renal inflammation and fibrosis. In conclusion, the results demonstrated that folate deficiency might aggravate inflammatory status and enhance renal fibrosis. |
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| language | English |
| last_indexed | 2024-03-10T23:40:14Z |
| publishDate | 2023-08-01 |
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| series | Nutrients |
| spelling | doaj.art-11e76a78de8546d49a3223d7b948d1fe2023-11-19T02:30:42ZengMDPI AGNutrients2072-66432023-08-011516361610.3390/nu15163616Folate Deficiency Enhanced Inflammation and Exacerbated Renal Fibrosis in High-Fat High-Fructose Diet-Fed MiceChun-Wai Chan0Bi-Fong Lin1Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei 10617, TaiwanDepartment of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei 10617, TaiwanThe prevalence of obesity and chronic kidney disease (CKD) is increasing simultaneously and rapidly worldwide. Our previous study showed that folate deficiency increased lipid accumulation and leptin production of adipocytes. Whether folate plays a role in CKD, particularly obesity-related nephropathy remains unclear. To investigate the effects of folate deficiency on CKD in diet-induced obese mice, four groups of male C57BL/6 mice were fed either a normal-fat diet (NF) with folate (NF+f); NF without folate (NF−f); high-fat high-fructose diet (HFF) with folate (HFF+f); or HFF without folate (HFF−f) for 12 months during the study. The results showed that HFF increased not only body weight, fasting blood glucose, total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol, and blood pressure, but also cytokines levels, such as interleukin (IL)-2, interferon (IFN)-γ, IL-17A/F, IL-6, monocyte chemoattractant protein (MCP)-1, and transforming growth factor (TGF)-β1. The indicators of kidney failure including urinary protein, neutrophil gelatinase-associated lipocalin (NGAL), renal type I and IV collagen deposits and leptin content, and serum creatinine were also increased by HFF. Folate-deficient diets further elevated serum TC, LDL-cholesterol, IL-6, tumor necrosis factor (TNF)-α, MCP-1, TGF-β1, and leptin, but decreased IL-10 level, and thus exacerbated renal fibrosis. To investigate the possible mechanisms of folate deficiency on renal injury, phosphorylation of pro-fibrosis signaling molecules, including signal transducer and activator of transcription (STAT)3 and small mothers against decapentaplegic (Smad)2/3, were assayed. Both HFF and folate deficiency significantly increased the phosphorylation of STAT3 and Smad2/3, suggesting synergistic effects of HFF−f on chronic renal inflammation and fibrosis. In conclusion, the results demonstrated that folate deficiency might aggravate inflammatory status and enhance renal fibrosis.https://www.mdpi.com/2072-6643/15/16/3616folate deficiencyleptinchronic inflammationfibrosisobesity-related nephropathy |
| spellingShingle | Chun-Wai Chan Bi-Fong Lin Folate Deficiency Enhanced Inflammation and Exacerbated Renal Fibrosis in High-Fat High-Fructose Diet-Fed Mice Nutrients folate deficiency leptin chronic inflammation fibrosis obesity-related nephropathy |
| title | Folate Deficiency Enhanced Inflammation and Exacerbated Renal Fibrosis in High-Fat High-Fructose Diet-Fed Mice |
| title_full | Folate Deficiency Enhanced Inflammation and Exacerbated Renal Fibrosis in High-Fat High-Fructose Diet-Fed Mice |
| title_fullStr | Folate Deficiency Enhanced Inflammation and Exacerbated Renal Fibrosis in High-Fat High-Fructose Diet-Fed Mice |
| title_full_unstemmed | Folate Deficiency Enhanced Inflammation and Exacerbated Renal Fibrosis in High-Fat High-Fructose Diet-Fed Mice |
| title_short | Folate Deficiency Enhanced Inflammation and Exacerbated Renal Fibrosis in High-Fat High-Fructose Diet-Fed Mice |
| title_sort | folate deficiency enhanced inflammation and exacerbated renal fibrosis in high fat high fructose diet fed mice |
| topic | folate deficiency leptin chronic inflammation fibrosis obesity-related nephropathy |
| url | https://www.mdpi.com/2072-6643/15/16/3616 |
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