Synergistic effects of polyphenols with leucine and β‐hydroxy‐ β‐methylbutyrate (HMB) on energy metabolism

Abstract

We recently demonstrated synergy between low dose resveratrol (200 nM) with leucine or its metabolite HMB on energy metabolism. We have now assessed potential synergy of other polyphenols with leucine and HMB. Dose‐response curves for fatty acid oxidation (FAO) were constructed and the highest non‐effective dose (typically 1 – 10 nM) was combined with either leucine (0.5 mM) or HMB (5 μM) to treat adipocytes and myotubes for 24h. Significant synergy was detected for the stilbenes (resveratrol, piceatannol) and a stilbene‐containing grape seed extract, resulting in stimulation of FAO in adipocytes (60–70%, p<0.05) and myotubes (>;2000%, p<0.01) and stimulation of AMPK (~50%, p<0.03) and Sirt1 (~65%, p<0.001) activities. Hydroxycinnamic acids, including chlorogenic and cinnamic acids and their derivatives, exhibited robust synergy with leucine and HMB, increasing FAO (300–1300% p<0.01), AMPK activity (~50%–150%, p<0.01), Sirt1 activity (~70%, p<0.001) and insulin sensitivity/glucose utilization (~50 – 150%, p<0.05). In contrast, more complex polyphenol structures (ellagic acid, epigallocatechin gallate) required higher concentrations (>;1 μM) and exerted little or no synergy with leucine or HMB. These data indicate synergy of several naturally occurring polyphenols with leucine or HMB in concentrations which produce no independent effects and are readily achievable via dietary supplementation.