n-lactoyl-phenylalanine

N-lactoyl-phenylalanine (Lac-Phe) is an exercise-induced metabolite, often referred to as an "exerkine," that is synthesized through the condensation of lactate and phenylalanine by the enzyme carnosine dipeptidase 2 (CNDP2). Originally identified as a circulating molecule that increases significantly after intense physical activity, Lac-Phe acts as a potent metabolic regulator and appetite suppressor. Its primary mechanism involves the inhibition of Agouti-related protein (AgRP)-expressing neurons in the hypothalamus by activating ATP-sensitive potassium (KATP) channels, which leads to reduced food intake and weight loss. Beyond its role in energy homeostasis, Lac-Phe exhibits anti-inflammatory properties by suppressing the NF-κB signaling pathway and M1 macrophage polarization. It also modulates lipid metabolism via the AMPK-PGC1α-PPARγ signaling axis, showing therapeutic potential in conditions such as obesity, type 2 diabetes, inflammatory bowel disease (IBD), and spinal cord injury recovery. Furthermore, it has been identified in fermented foods and studied as a biomarker for mitochondrial dysfunction.

Other names

Lac-PheL-PN-Lactoyl-L-phenylalanine