Bovine α-lactalbumin-derived peptides attenuate TNF-α-induced insulin resistance and inflammation in 3T3-L1 adipocytes through inhibiting JNK and NF-κB signaling

Bioactive peptides in bovine alpha-lactalbumin were isolated and identified, and the effects and mechanisms of peptide KILDK on insulin resistance in 3T3-L1 adipocytes were investigated. Mature 3T3-L1 adipocytes were stimulated with TNF-alpha to induce insulin resistance. Bovine alpha-lactalbumin hydrolysates (alpha-LAH) were subjected to stimulated gastrointestinal digestion and Caco-2 absorption, and GD-alpha-LAH and CA-alpha-LAH were obtained. Our results demonstrated that alpha-LAH, GD-alpha-LAH, and CA-alpha-LAH increased glucose uptake, enhanced Akt phosphorylation (Ser473), and decreased IRS-1 phosphorylation (Ser307) in insulin resistant 3T3-L1 adipocytes. Gel filtration chromatography and liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI MS/MS) were used to separate and identify bioactive peptides. The identified peptide KILDK attenuated insulin resistance in 3T3-L1 adipocytes, which was attributed to the suppression of JNK phosphorylation (Thr183/Tyr185). Moreover, KILDK downregulated pro-inflammatory genes through blocking NF-kappa B signaling. Our findings suggested that bovine alpha-LAH might be a potential ingredient against insulin resistance.

Automated summary

Bioactive peptides in bovine alpha-lactalbumin were isolated and identified. One of these peptides, KILDK, was found to attenuate insulin resistance in adipocytes by suppressing a specific signaling pathway and downregulating the expression of pro-inflammatory genes.