title: PRDM16 sustains white fat gene expression profile in human adipocytes in direct relation with insulin action.
abstract: 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 µmol/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.
authors: Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010), Instituto de Salud Carlos III (ISCIII), Girona 17007, Spain. Electronic address: jmoreno@idibgi.org.
authors: José María
authors: JM
authors: Moreno-Navarrete
authors: Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010), Instituto de Salud Carlos III (ISCIII), Girona 17007, Spain.
authors: Francisco
authors: F
authors: Ortega
authors: Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010), Instituto de Salud Carlos III (ISCIII), Girona 17007, Spain.
authors: María
authors: M
authors: Moreno
authors: Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010), Instituto de Salud Carlos III (ISCIII), Girona 17007, Spain.
authors: Gemma
authors: G
authors: Xifra
authors: Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010), Instituto de Salud Carlos III (ISCIII), Girona 17007, Spain.
authors: Wifredo
authors: W
authors: Ricart
authors: Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010), Instituto de Salud Carlos III (ISCIII), Girona 17007, Spain. Electronic address: jmfreal@idibgi.org.
authors: José Manuel
authors: JM
authors: Fernández-Real
mesh_terms: D052438:Adipocytes, White / Q000378:metabolism*; D050156:Adipogenesis; D052436:Adipose Tissue, White / Q000378:metabolism / Q000473:pathology; D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005260:Female; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000494:pharmacology; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D059467:Transcriptome
chemical_list: D004268:DNA-Binding Proteins; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; C416371:PRDM16 protein, human; C495692:SLC2A4 protein, human; D014157:Transcription Factors; D008687:Metformin
keywords: Adipogenesis; Human adipose tissue; Insulin sensitivity; Obesity; PRDM16