We have located links that may give you full text access.
1,25-dihydroxyvitamin D 3 affects thapsigargin-induced endoplasmic reticulum stress in 3T3-L1 adipocytes.
Nutrition Research and Practice 2024 Februrary
BACKGROUND/OBJECTIVES: Endoplasmic reticulum (ER) stress in adipose tissue causes an inflammatory response and leads to metabolic diseases. However, the association between vitamin D and adipose ER stress remains poorly understood. In this study, we investigated whether 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) alleviates ER stress in adipocytes.
MATERIALS/METHODS: 3T3-L1 cells were treated with different concentrations (i.e., 10-100 nM) of 1,25(OH)2 D3 after or during differentiation (i.e., on day 0-7, 3-7, or 7). They were then incubated with thapsigargin (TG, 500 nM) for an additional 24 h to induce ER stress. Next, we measured the mRNA and protein levels of genes involved in unfold protein response (UPR) and adipogenesis using real-time polymerase chain reaction and western blotting and quantified the secreted protein levels of pro-inflammatory cytokines. Finally, the mRNA levels of UPR pathway genes were measured in adipocytes transfected with siRNA-targeting Vdr .
RESULTS: Treatment with 1,25(OH)2 D3 during various stages of adipocyte differentiation significantly inhibited ER stress induced by TG. In fully differentiated 3T3-L1 adipocytes, 1,25(OH)2 D3 treatment suppressed mRNA levels of Ddit3 , sXbp1 , and Atf4 and decreased the secretion of monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-α. However, downregulation of the mRNA levels of Ddit3 , sXbp1 , and Atf4 following 1,25(OH)2 D3 administration was not observed in Vdr -knockdown adipocytes. In addition, exposure of 3T3-L1 preadipocytes to 1,25(OH)2 D3 inhibited transcription of Ddit3 , sXbp1 , Atf4 , Bip , and Atf6 and reduced the p-alpha subunit of translation initiation factor 2 (eIF2α)/eIF2α and p-protein kinase RNA-like ER kinase (PERK)/PERK protein ratios. Furthermore, 1,25(OH)2 D3 treatment before adipocyte differentiation reduced adipogenesis and the mRNA levels of adipogenic genes.
CONCLUSIONS: Our data suggest that 1,25(OH)2 D3 prevents TG-induced ER stress and inflammatory responses in mature adipocytes by downregulating UPR signaling via binding with Vdr . In addition, the inhibition of adipogenesis by vitamin D may contribute to the reduction of ER stress in adipocytes.
MATERIALS/METHODS: 3T3-L1 cells were treated with different concentrations (i.e., 10-100 nM) of 1,25(OH)2 D3 after or during differentiation (i.e., on day 0-7, 3-7, or 7). They were then incubated with thapsigargin (TG, 500 nM) for an additional 24 h to induce ER stress. Next, we measured the mRNA and protein levels of genes involved in unfold protein response (UPR) and adipogenesis using real-time polymerase chain reaction and western blotting and quantified the secreted protein levels of pro-inflammatory cytokines. Finally, the mRNA levels of UPR pathway genes were measured in adipocytes transfected with siRNA-targeting Vdr .
RESULTS: Treatment with 1,25(OH)2 D3 during various stages of adipocyte differentiation significantly inhibited ER stress induced by TG. In fully differentiated 3T3-L1 adipocytes, 1,25(OH)2 D3 treatment suppressed mRNA levels of Ddit3 , sXbp1 , and Atf4 and decreased the secretion of monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-α. However, downregulation of the mRNA levels of Ddit3 , sXbp1 , and Atf4 following 1,25(OH)2 D3 administration was not observed in Vdr -knockdown adipocytes. In addition, exposure of 3T3-L1 preadipocytes to 1,25(OH)2 D3 inhibited transcription of Ddit3 , sXbp1 , Atf4 , Bip , and Atf6 and reduced the p-alpha subunit of translation initiation factor 2 (eIF2α)/eIF2α and p-protein kinase RNA-like ER kinase (PERK)/PERK protein ratios. Furthermore, 1,25(OH)2 D3 treatment before adipocyte differentiation reduced adipogenesis and the mRNA levels of adipogenic genes.
CONCLUSIONS: Our data suggest that 1,25(OH)2 D3 prevents TG-induced ER stress and inflammatory responses in mature adipocytes by downregulating UPR signaling via binding with Vdr . In addition, the inhibition of adipogenesis by vitamin D may contribute to the reduction of ER stress in adipocytes.
Full text links
Related Resources
Trending Papers
Review article: Recent advances in ascites and acute kidney injury management in cirrhosis.Alimentary Pharmacology & Therapeutics 2024 March 26
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app