The role of C16:0 ceramide in the development of obesity and type 2 diabetes: CerS6 inhibition as a novel therapeutic approach.

•Designed, screened and discovered therapeutic CerS6 ASO that specifically and selectively inhibits CerS6 in in-vivo.•Therapeutic inhibition of a selective enzyme (CerS6) ameliorate insulin resistance and hyperglycemia.•In-vivo selective ablation of CerS6 protected from body weight gain (∼25% body weight reduction in HFD obese mice).•CerS6 could be a potentially attractive target for the treatment of insulin resistance, obesity and type 2 diabetes.