PMID- 25662275 OWN - NLM STAT- MEDLINE DCOM- 20151221 LR - 20150317 IS - 1872-8057 (Electronic) IS - 0303-7207 (Linking) VI - 405 DP - 2015 Apr 15 TI - PRDM16 sustains white fat gene expression profile in human adipocytes in direct relation with insulin action. PG - 84-93 LID - S0303-7207(15)00066-0 [pii] LID - 10.1016/j.mce.2015.01.042 [doi] AB - In the present study, we aimed to evaluate the possible role of PRDM16 in human adipocytes and in whole adipose tissue according to obesity and insulin sensitivity. PRDM16 knockdown (KD) had a dual behavior. While KD in preadipocytes led to enhanced gene expression markers of adipocyte differentiation, PRDM16 KD in fully differentiated adipocytes resulted in decreased adipogenic gene expression and insulin action. In line with KD in adipocytes, PRDM16 was positively associated with the expression of several genes involved in adipogenesis, insulin signaling, mitochondrial function and brown adipocyte-related markers in whole adipose tissue from two independent cohorts. PRDM16 was decreased in obese subjects in relation with the decrease of insulin sensitivity [HOM(AIR) (cohort 1) and M clamp value (cohort 2)]. Rosiglitazone (5 micromol/l) and metformin (5 mmol/l) led to increased PRDM16 mRNA and protein levels in isolated human adipocytes and in whole adipose tissue. In conclusion, PRDM16 might contribute to maintain adipose tissue "white fat" gene expression profile and systemic metabolic homeostasis. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. 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), Instituto de Salud Carlos III (ISCIII), Girona 17007, Spain. Electronic address: jmoreno@idibgi.org. FAU - Ortega, Francisco AU - Ortega F AD - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio Biomedica de Girona (IdIBGi), CIBEROBN (CB06/03/010), Instituto de Salud Carlos III (ISCIII), Girona 17007, Spain. FAU - Moreno, Maria AU - Moreno M AD - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio Biomedica de Girona (IdIBGi), CIBEROBN (CB06/03/010), Instituto de Salud Carlos III (ISCIII), Girona 17007, Spain. FAU - Xifra, Gemma AU - Xifra G AD - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio Biomedica de Girona (IdIBGi), CIBEROBN (CB06/03/010), Instituto de Salud Carlos III (ISCIII), Girona 17007, Spain. FAU - Ricart, Wifredo AU - Ricart W AD - Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigacio Biomedica de Girona (IdIBGi), CIBEROBN (CB06/03/010), Instituto de Salud Carlos III (ISCIII), Girona 17007, 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), Instituto de Salud Carlos III (ISCIII), Girona 17007, Spain. Electronic address: jmfreal@idibgi.org. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150207 PL - Ireland TA - Mol Cell Endocrinol JT - Molecular and cellular endocrinology JID - 7500844 RN - 0 (DNA-Binding Proteins) RN - 0 (Glucose Transporter Type 4) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (PRDM16 protein, human) RN - 0 (SLC2A4 protein, human) RN - 0 (Transcription Factors) RN - 9100L32L2N (Metformin) SB - IM MH - Adipocytes, White/*metabolism MH - Adipogenesis MH - Adipose Tissue, White/metabolism/pathology MH - Adult MH - Case-Control Studies MH - Cells, Cultured MH - DNA-Binding Proteins/*physiology MH - Diabetes Mellitus, Type 2/metabolism MH - Female MH - Glucose Transporter Type 4/metabolism MH - Homeostasis MH - Humans MH - Hypoglycemic Agents/pharmacology MH - Insulin/*physiology MH - Insulin Resistance MH - Male MH - Metformin/pharmacology MH - Middle Aged MH - Obesity/metabolism MH - Transcription Factors/*physiology MH - *Transcriptome OTO - NOTNLM OT - Adipogenesis OT - Human adipose tissue OT - Insulin sensitivity OT - Obesity OT - PRDM16 EDAT- 2015/02/11 06:00 MHDA- 2015/12/22 06:00 CRDT- 2015/02/10 06:00 PHST- 2014/10/13 00:00 [received] PHST- 2015/01/22 00:00 [revised] PHST- 2015/01/29 00:00 [accepted] PHST- 2015/02/10 06:00 [entrez] PHST- 2015/02/11 06:00 [pubmed] PHST- 2015/12/22 06:00 [medline] AID - S0303-7207(15)00066-0 [pii] AID - 10.1016/j.mce.2015.01.042 [doi] PST - ppublish SO - Mol Cell Endocrinol. 2015 Apr 15;405:84-93. doi: 10.1016/j.mce.2015.01.042. Epub 2015 Feb 7.