Effect of β‐Hydroxy β‐methylbutyric acid on macrophage polarization

Abstract

β‐Hydroxy β‐methylbutyric acid (HMB) is a metabolite of the essential amino acid leucine and can be detected in the circulation at low μM levels during fasting. HMB exerts metabolic effects by enhancing mitochondrial biogenesis and fatty acid oxidation and it also protects skeletal muscle by promoting protein synthesis and suppressing protein degradation. Macrophages make up a crucial part of innate immune system, and growing evidence suggests that they are responsive to the metabolic environment and its dysregulation which occurs with obesity, diabetes and aging. Macrophages are often classified as being pro‐inflammatory M1‐like and anti‐inflammatory M2‐like. Here, we used THP‐1 macrophages to investigate the effect of HMB on macrophage polarization. Macrophages were differentiated with PMA (M0) and then polarized to M1 or M2. Cells were stimulated with IFNγ and LPS for M1 polarization, and were stimulated with IL‐4 for M2 polarization. TNF mRNA modestly decreased (p=0.05) in M1 macrophages and IL‐10 mRNA increased (p<0.05) in M2 macrophages after co‐treatment with 5 μM HMB for 24 hours during polarization. These results suggest that low concentrations of HMB may play a modest role in modulating macrophage gene expression in response to polarizing cytokines.