Methylated Medium‐ and Long‐Chain Fatty Acids Provide Novel Sources of Anaplerotic Carbon for Fasting or Exercising Mice (LB438)

Abstract

We hypothesized that methylated fatty acids (e.g. 2‐methylpentanoic acid (2MeP), phytanic or pristanic acids) would provide anaplerotic carbon to the tricarboxylic acid (TCA) cycle and thereby enhance fatty acid oxidation, especially under conditions when TCA cycle intermediates are depleted. The optimal dose of 2MeP and pristanic acid for increasing in vitro [1‐14C]‐oleic acid oxidation in liver or skeletal muscle homogenates from fasted mice (n=4) was assessed using doses of 0, 0.25, 0.5, 0.75, or 1.0 mM. The minimum dose (0.25 mM) maximally stimulated liver tissue oxidation of [1‐14C]‐oleate to 14CO2 by 2‐fold (P < 0.05), but no stimulation was detected in muscle. Similar incubations with 0.25 mM 2MeP, hexanoate, palmitate, phytanic acid, or pristanic acid or 0.1 mM malate or propionyl‐CoA were conducted with liver and skeletal muscle homogenates from acutely exercised or sedentary mice. Regardless of exercise, incubation of liver homogenates with 2MeP increased [1‐14C]‐oleate oxidation to 14CO2 by 60% over control incubations containing hexanoate (P < 0.05). Phytanic acid treatment increased [14C]‐acid‐soluble product accumulation in liver tissue as compared to palmitate (P < 0.05). Anaplerotic stimulation was unaffected by exercised state (P > 0.05) and not evidenced in muscle homogenates. Results were consistent with our hypothesis that methyl‐branched fatty acids may provide anaplerotic carbon and thereby stimulate in vitro fatty acid oxidation.Grant Funding Source: North Carolina Agricultural Research Service and by USDA‐AFRI training grant # 2010‐65200‐20354