Novel anti-obesity peptide (RLLPH) derived from hazelnut (Corylus heterophylla Fisch) protein hydrolysates inhibits adipogenesis in 3T3-L1 adipocytes by regulating adipogenic transcription factors and adenosine monophosphate-activated protein kinase (AMPK) activation.

Hazelnut proteins are an excellent source of bioactive peptides. Our previous study demonstrated that several novel peptides derived from Corylus heterophylla Fisch (C. heterophylla Fisch) have antioxidant and anti-inflammatory activities. In this study, we purified and identified anti-obesity peptides from hazelnut protein hydrolysates by chromatography and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Subsequently, we evaluated the inhibitory effect of the synthetic peptide on adipogenesis in 3T3-L1 adipocytes by Oil Red O staining, reverse transcription polymerase chain reaction (RT-PCR) and western blot. The results showed that a novel synthetic pentapeptide, Arg-Leu-Leu-Pro-His (RLLPH), derived from the C3 fraction, attenuated adipogenesis by downregulating the expression of several mRNAs related to adipogenesis, including peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein alpha (C/EBPα), adipocyte fatty acid-binding protein 2 (aP2), sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA carboxylase 1 (ACC1), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Moreover, RLLPH upregulated the levels of phosphorylated Adenosine monophosphate-activated protein kinase (AMPK) and its substrate acetyl-CoA carboxylase (ACC) in 3T3-L1 adipocytes. A stability study revealed that RLLPH was relatively stable during pepsin digestion. These findings suggest that RLLPH has potential anti-obesity effects and may help combat metabolic diseases.