PRDM16 sustains white fat gene expression profile in human adipocytes in direct relation with insulin action

• PRDM16 knockdown (KD) in human subcutaneous preadipocytes led to enhanced adipocyte differentiation.
• PRDM16 knockdown (KD) in human fully differentiated adipocytes resulted in decreased adipogenic gene expression.
• PRDM16 levels were associated with adipogenesis, insulin signaling and mitochondrial function in human adipose tissue.
• Adipose tissue PRDM16 mRNA was decreased in association with obesity and insulin resistance measures.
• Metformin led to increased PRDM16 mRNA in whole adipose tissue and in isolated human adipocytes.

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 [HOMAIR (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.