PMID- 36206624 OWN - NLM STAT- MEDLINE DCOM- 20221120 LR - 20230104 IS - 2352-3964 (Electronic) IS - 2352-3964 (Linking) VI - 85 DP - 2022 Nov TI - Adipose tissue cysteine dioxygenase type 1 is associated with an anti-inflammatory profile, impacting on systemic metabolic traits. PG - 104302 LID - S2352-3964(22)00484-4 [pii] LID - 10.1016/j.ebiom.2022.104302 [doi] LID - 104302 AB - BACKGROUND: Adipose tissue is a source of multiple factors that modulate systemic insulin sensitivity and cardiovascular risk. Taurine is obtained from the diet but it is less known that it is endogenously synthesized by cysteine dioxygenase type 1 (CDO1). CDO1 exerts a role in adipose tissue from rodent models, but the potential translational value in humans is not available in the literature. METHODS: CDO1 gene expression was analysed in visceral and subcutaneous adipose tissue samples in association with metabolic traits in participants with different degrees of obesity in four independent cohorts. CDO1 was also evaluated in isolated human adipocytes in vitro. Mechanistically, CDO1gene knockdown (KD) of human preadipocytes and adipose-derived mesenchymal stem cells (ASC52telo) (using lentiviral particles) was also evaluated. Mitochondrial respiratory function of adipocytes was evaluated using Seahorse. FINDINGS: Both visceral (VAT) and subcutaneous adipose tissue (SAT) CDO1 mRNA was associated with gene expression markers of adipose tissue function in the four cohorts. Higher CDO1 expression was linked to decreased fasting triglycerides and blood HbA1c even after adjusting by age, BMI and sex. In addition, CDO1 mRNA positively correlated with the expression of genes involved in adipogenesis and negatively with different inflammatory markers. Both VAT and SAT CDO1 mRNA was mainly expressed in adipocytes and significantly increased during adipocyte differentiation, but attenuated under inflammatory conditions. Mechanistically, CDO1 gene KD reduced taurine biosynthesis, evidencing lower CDO1 activity. In both human preadipocytes and ASC52telo cells, CDO1 gene KD resulted in decreased gene expression markers of adipogenesis (ADIPOQ, FABP4, FASN, SLC2A4, CEBPA) and increased inflammatory genes (TNF and IL6) during adipocyte differentiation. Of note, CDO1 gene KD led to decreased mitochondrial respiratory function in parallel to decreased expression of mitochondrial function-, but not biogenesis-related genes. INTERPRETATION: Current findings show the relevance of CDO1 in adipose tissue physiology, suggesting its contribution to an improved systemic metabolic profile. FUNDING: This work was partially supported by research grants PI16/01173, PI19/01712, PI20/01090 and PI21/01361 from the Instituto de Salud Carlos III from Spain, Fondo Europeo de Desarrollo Regional (FEDER) funds, and VII Spanish Diabetes Association grants to Basic Diabetes Research Projects led by young researchers. CI - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Latorre, Jessica AU - Latorre J AD - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio Biomedica de Girona (IdIBGi), CIBEROBN (CB06/03/010), 17190 Salt, Spain; CIBER de la Fisiopatologia de la Obesidad y Nutricion (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain. FAU - Mayneris-Perxachs, Jordi AU - Mayneris-Perxachs J AD - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio Biomedica de Girona (IdIBGi), CIBEROBN (CB06/03/010), 17190 Salt, Spain; CIBER de la Fisiopatologia de la Obesidad y Nutricion (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain. FAU - Oliveras-Canellas, Nuria AU - Oliveras-Canellas N AD - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio Biomedica de Girona (IdIBGi), CIBEROBN (CB06/03/010), 17190 Salt, Spain; CIBER de la Fisiopatologia de la Obesidad y Nutricion (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain. FAU - Ortega, Francisco AU - Ortega F AD - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio Biomedica de Girona (IdIBGi), CIBEROBN (CB06/03/010), 17190 Salt, Spain; CIBER de la Fisiopatologia de la Obesidad y Nutricion (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain. FAU - Comas, Ferran AU - Comas F AD - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio Biomedica de Girona (IdIBGi), CIBEROBN (CB06/03/010), 17190 Salt, Spain; CIBER de la Fisiopatologia de la Obesidad y Nutricion (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain. FAU - Fernandez-Real, Jose Manuel AU - Fernandez-Real JM AD - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio Biomedica de Girona (IdIBGi), CIBEROBN (CB06/03/010), 17190 Salt, Spain; CIBER de la Fisiopatologia de la Obesidad y Nutricion (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain; Department of Medical Sciences, School of Medicine, University of Girona, 17071 Girona, Spain. Electronic address: jmfreal@idibgi.org. FAU - Moreno-Navarrete, Jose Maria AU - Moreno-Navarrete JM AD - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio Biomedica de Girona (IdIBGi), CIBEROBN (CB06/03/010), 17190 Salt, Spain; CIBER de la Fisiopatologia de la Obesidad y Nutricion (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain. Electronic address: jmoreno@idibgi.org. LA - eng PT - Journal Article DEP - 20221004 PL - Netherlands TA - EBioMedicine JT - EBioMedicine JID - 101647039 RN - 0 (Anti-Inflammatory Agents) RN - EC 1.13.11.20 (Cysteine Dioxygenase) RN - 0 (RNA, Messenger) RN - 1EQV5MLY3D (Taurine) RN - EC 1.13.11.20 (CDO1 protein, human) SB - IM CIN - EBioMedicine. 2022 Dec;86:104332. PMID: 36335668 MH - Humans MH - Adipogenesis/genetics MH - *Adipose Tissue/metabolism MH - Anti-Inflammatory Agents/metabolism MH - Cells, Cultured MH - *Cysteine Dioxygenase/genetics/metabolism MH - RNA, Messenger/genetics MH - Taurine/metabolism PMC - PMC9535416 OTO - NOTNLM OT - Adipogenesis OT - Adipose tissue OT - Inflammation OT - Obesity OT - Taurine COIS- Declaration of interests The authors declared no conflict of interest. EDAT- 2022/10/08 06:00 MHDA- 2022/11/16 06:00 PMCR- 2022/10/04 CRDT- 2022/10/07 18:17 PHST- 2022/07/05 00:00 [received] PHST- 2022/08/11 00:00 [revised] PHST- 2022/09/21 00:00 [accepted] PHST- 2022/10/08 06:00 [pubmed] PHST- 2022/11/16 06:00 [medline] PHST- 2022/10/07 18:17 [entrez] PHST- 2022/10/04 00:00 [pmc-release] AID - S2352-3964(22)00484-4 [pii] AID - 104302 [pii] AID - 10.1016/j.ebiom.2022.104302 [doi] PST - ppublish SO - EBioMedicine. 2022 Nov;85:104302. doi: 10.1016/j.ebiom.2022.104302. Epub 2022 Oct 4.