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MON-598 Vitamin B12 Deficiency Leads to Fatty Acid Metabolism Dysregulation and Increased Pro-Inflammatory Cytokine Production in Human Adipocytes and Maternal Subcutaneous and Omental Adipose Tissue

Vitamin B12 (B12) is an essential micronutrient required for optimal hematopoietic, neurologic and other several metabolic reactions. Animal and clinical studies show that B12-deficiency is associated with maternal obesity, insulin resistance, and metabolic syndrome. Given the key metabolic role of...

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Autores principales: Samavat, Jinous, Adaikalakoteswari, Antonysunil, Boachie, Joseph, McTernan, Philip, Christian, Mark, Saravanan, Ponnusamy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7208500/
http://dx.doi.org/10.1210/jendso/bvaa046.1803
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author Samavat, Jinous
Adaikalakoteswari, Antonysunil
Boachie, Joseph
McTernan, Philip
Christian, Mark
Saravanan, Ponnusamy
author_facet Samavat, Jinous
Adaikalakoteswari, Antonysunil
Boachie, Joseph
McTernan, Philip
Christian, Mark
Saravanan, Ponnusamy
author_sort Samavat, Jinous
collection PubMed
description Vitamin B12 (B12) is an essential micronutrient required for optimal hematopoietic, neurologic and other several metabolic reactions. Animal and clinical studies show that B12-deficiency is associated with maternal obesity, insulin resistance, and metabolic syndrome. Given the key metabolic role of adipose tissue, we investigated whether B12 deficiency may affect triglyceride synthesis and lipid metabolism leading to adipose tissue inflammation. The AbdSc pre-adipocyte cell line (Chub-S7) and human AbdSc primary pre-adipocytes were differentiated under different B12 concentrations (25pM,100pM,1nM,500nM). Human Om, Sc-AT and blood samples were collected from 106 pregnant women at delivery. SerumB12 and relevant metabolic risk factors were measured. Gene expression was performed by q-RTPCR, de novo triglyceride synthesis was quantified by radioactive tracing, ß-oxidation and palmitate-induced oxygen consumption rate was determined using seahorse-XF analyser. Adipocytes cultured in low-B12 conditions showed significantly increased expression (P<0.01) of triglyceride biosynthesis genes (ELOVL6,SCD,GPAT,LPIN1 and DGAT2), a significantly decreased expression (P<0.01) of ß-oxidation genes (FAT/CD36,CPT1-ß,ACADL,ECHS1 andACAA2) and an increased expression (P<0.01) of pro-inflammatory cytokines (IL-1, IL-6,IL-8,IL-18,TGF-β,TNF-α and MCP-1). These data were also confirmed in the AT of B12-deficient pregnant women. Additionally, real-time fatty acid flux synthesis and fatty-acid-oxidation induced by palmitate were significantly altered (P<0.05) in B12-deficient adipocytes. Our data highlights that B12-deficiency has profound effects on adipocyte dysfunction, opening new insights into the pathogenesis of maternal obesity and the relevance of micronutrient supplementation for pregnant mothers.
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spelling pubmed-72085002020-05-13 MON-598 Vitamin B12 Deficiency Leads to Fatty Acid Metabolism Dysregulation and Increased Pro-Inflammatory Cytokine Production in Human Adipocytes and Maternal Subcutaneous and Omental Adipose Tissue Samavat, Jinous Adaikalakoteswari, Antonysunil Boachie, Joseph McTernan, Philip Christian, Mark Saravanan, Ponnusamy J Endocr Soc Adipose Tissue, Appetite, and Obesity Vitamin B12 (B12) is an essential micronutrient required for optimal hematopoietic, neurologic and other several metabolic reactions. Animal and clinical studies show that B12-deficiency is associated with maternal obesity, insulin resistance, and metabolic syndrome. Given the key metabolic role of adipose tissue, we investigated whether B12 deficiency may affect triglyceride synthesis and lipid metabolism leading to adipose tissue inflammation. The AbdSc pre-adipocyte cell line (Chub-S7) and human AbdSc primary pre-adipocytes were differentiated under different B12 concentrations (25pM,100pM,1nM,500nM). Human Om, Sc-AT and blood samples were collected from 106 pregnant women at delivery. SerumB12 and relevant metabolic risk factors were measured. Gene expression was performed by q-RTPCR, de novo triglyceride synthesis was quantified by radioactive tracing, ß-oxidation and palmitate-induced oxygen consumption rate was determined using seahorse-XF analyser. Adipocytes cultured in low-B12 conditions showed significantly increased expression (P<0.01) of triglyceride biosynthesis genes (ELOVL6,SCD,GPAT,LPIN1 and DGAT2), a significantly decreased expression (P<0.01) of ß-oxidation genes (FAT/CD36,CPT1-ß,ACADL,ECHS1 andACAA2) and an increased expression (P<0.01) of pro-inflammatory cytokines (IL-1, IL-6,IL-8,IL-18,TGF-β,TNF-α and MCP-1). These data were also confirmed in the AT of B12-deficient pregnant women. Additionally, real-time fatty acid flux synthesis and fatty-acid-oxidation induced by palmitate were significantly altered (P<0.05) in B12-deficient adipocytes. Our data highlights that B12-deficiency has profound effects on adipocyte dysfunction, opening new insights into the pathogenesis of maternal obesity and the relevance of micronutrient supplementation for pregnant mothers. Oxford University Press 2020-05-08 /pmc/articles/PMC7208500/ http://dx.doi.org/10.1210/jendso/bvaa046.1803 Text en © Endocrine Society 2020. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Adipose Tissue, Appetite, and Obesity
Samavat, Jinous
Adaikalakoteswari, Antonysunil
Boachie, Joseph
McTernan, Philip
Christian, Mark
Saravanan, Ponnusamy
MON-598 Vitamin B12 Deficiency Leads to Fatty Acid Metabolism Dysregulation and Increased Pro-Inflammatory Cytokine Production in Human Adipocytes and Maternal Subcutaneous and Omental Adipose Tissue
title MON-598 Vitamin B12 Deficiency Leads to Fatty Acid Metabolism Dysregulation and Increased Pro-Inflammatory Cytokine Production in Human Adipocytes and Maternal Subcutaneous and Omental Adipose Tissue
title_full MON-598 Vitamin B12 Deficiency Leads to Fatty Acid Metabolism Dysregulation and Increased Pro-Inflammatory Cytokine Production in Human Adipocytes and Maternal Subcutaneous and Omental Adipose Tissue
title_fullStr MON-598 Vitamin B12 Deficiency Leads to Fatty Acid Metabolism Dysregulation and Increased Pro-Inflammatory Cytokine Production in Human Adipocytes and Maternal Subcutaneous and Omental Adipose Tissue
title_full_unstemmed MON-598 Vitamin B12 Deficiency Leads to Fatty Acid Metabolism Dysregulation and Increased Pro-Inflammatory Cytokine Production in Human Adipocytes and Maternal Subcutaneous and Omental Adipose Tissue
title_short MON-598 Vitamin B12 Deficiency Leads to Fatty Acid Metabolism Dysregulation and Increased Pro-Inflammatory Cytokine Production in Human Adipocytes and Maternal Subcutaneous and Omental Adipose Tissue
title_sort mon-598 vitamin b12 deficiency leads to fatty acid metabolism dysregulation and increased pro-inflammatory cytokine production in human adipocytes and maternal subcutaneous and omental adipose tissue
topic Adipose Tissue, Appetite, and Obesity
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7208500/
http://dx.doi.org/10.1210/jendso/bvaa046.1803
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