The increasing prevalence of
obesity worldwide has become an alarming public health concern because of dramatic increases in the incidence of
obesity-associated diseases, including
type 2 diabetes mellitus (T2DM). Peripheral
insulin resistance and impaired insulin secretion remain the core defects in T2DM. Despite significant advances in unraveling the mechanisms underlying these defects, many of the metabolic pathways and regulators involved in
insulin resistance and β-cell dysfunction are not completely understood. This review proposes that manipulating the
fatty acid (FA) composition by blocking ELOVL
fatty acid elongase 6 (Elovl6) could protect against
insulin resistance, impaired insulin secretion, and
obesity-related disorders. Elovl6 is a microsomal
enzyme involved in the elongation of C16 saturated and monounsaturated FAs to form C18 FAs. We have reported that mice with Elovl6 deletion are protected against
obesity-induced
insulin resistance or β-cell failure because the cellular FA composition is changed, even with concurrent
obesity. Therefore, Elovl6 appears to be a crucial metabolic checkpoint, and limiting the expression or activity of Elovl6 could be a new therapeutic approach in the treatment of T2DM.