Abstract

ObjectiveFasting and postprandial metabolism are adversely affected by a sedentary lifestyle. However, the role of the prevailing diet remains unclear. The objective of the present study was to determine the influence of a high fat diet (HFD) on fasting and postprandial skeletal muscle substrate metabolism in sedentary compared with endurance trained (ET) humans.MethodsMetabolically healthy sedentary (n=17) and ET (n=7) males were control‐fed a 10‐day isocaloric moderate fat diet (30% fat [<10% saturated fat], 55% carbohydrate) followed by a 5‐day isocaloric HFD (55% fat [25% saturated fat], 30% carbohydrate). Before and after the HFD participants completed a high fat meal challenge (820 kcals; 63% fat [26% saturated fat], 25% carbohydrate) in which skeletal muscle biopsies were taken in the fasted and 4‐hour fed states. Complete fat, glucose, and pyruvate oxidation were assessed by measuring 14CO2 production in homogenized skeletal muscle incubated with radio‐labeled substrates. Incomplete fat oxidation was assessed by measuring 14C‐labeled acid soluble metabolites. Total fat oxidation was comprised of the sum of complete and incomplete fat oxidation. A substrate preference assay was performed by assessing the free fatty acid (FFA)‐induced suppression of [1‐14C]‐pyruvate oxidation. The meal effect for each substrate oxidation measure was calculated as the percent change from the fasted to 4‐hour fed state.ResultsThe meal effect for glucose oxidation was not altered by the HFD in the ET group (128 ± 92% vs. 41 ± 15%, P=0.375) but was reduced in the sedentary group (78 ± 26% vs. −21 ± 6%, P=0.002). The meal effect for pyruvate oxidation was similar between ET and sedentary groups before the HFD (34 ± 13% vs. 14 ± 17%, respectively; P=0.145) but was lower in the sedentary compared with the ET group after the HFD (−16 ± 6% vs. 24 ± 17%, P=0.047). The meal effect for substrate preference as indicated by FFA‐induced suppression of pyruvate oxidation was retained after the HFD in the ET group (20 ± 4% vs. 41 ± 21%, P=0.342) but was reduced in the sedentary group (34 ± 7% vs. 4 ± 5%, P=0.003). The meal effects for incomplete and total fat oxidation tended to decrease as a result of the HFD in the overall sample (P=0.075 and P=0.062, respectively). There were no physical activity group or HFD effects on meal effects for complete fat oxidation or the ratio of complete‐to‐incomplete fat oxidation.ConclusionsThese findings suggest skeletal muscle from sedentary individuals displays reduced postprandial glucose oxidation, yet pyruvate is preferred over fatty acids as an oxidative substrate following consumption of a HFD. These data highlight the need to better understand key regulatory nodes in skeletal muscle substrate metabolism between ET and sedentary humans.Support or Funding InformationADA‐07‐12 (MWH); Virginia Tech Translational Obesity Research IGEPThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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