Regular exercise is the first line of
therapy for treating
obesity-mediated metabolic disorders, including
insulin resistance. It has been reported that developmental endothelial locus-1 (DEL-1) enhances macrophage efferocytosis, resulting in
inflammation clearance as well as improves
insulin resistance in skeletal muscle. However, the relationship between exercise and DEL-1, and the effects of DEL-1 on
insulin signalling in adipocytes have not been fully elucidated to date.
Protein expression levels were determined by Western blot analysis. Cells were transfected with small interfering (si)
RNA to suppress gene expression.
Lipid accumulation levels were detected using
Oil red-O staining. Proinflammatory
cytokine secretion levels were measured using ELISA. DEL-1 expression levels were induced in the skeletal muscle of people who exercised using microarray analysis. Recombinant DEL-1 augmented
AMP-activated protein kinase (AMPK) phosphorylation and
haem oxygenase (HO)-1 expression to alleviating
inflammation and impairment of
insulin signalling in 3T3-L1 adipocytes treated with
palmitate.
siRNA of AMPK or HO-1 also mitigated the effects of DEL-1 on
inflammation and
insulin resistance. DEL-1 ameliorates
inflammation and
insulin resistance in differentiated 3T3-L1 cells via AMPK/HO-1 signalling, suggesting that DEL-1 may be the exercise-mediated therapeutic target for treating
insulin resistance and
type 2 diabetes.