Physical inactivity differentially alters dietary oleate and palmitate trafficking

Abstract

Objective: Obesity and diabetes are characterized by the incapacity to use fat as fuel. We hypothesized that this reduced fat oxidation is secondary to a sedentary lifestyle.

Research design and methods: We investigated the effect of a 2-month bed rest on the dietary oleate and palmitate trafficking in lean women (control group, n = 8) and the effect of concomitant resistance/aerobic exercise training as a countermeasure (exercise group, n = 8). Trafficking of stable isotope-labeled dietary fats was combined with muscle gene expression and magnetic resonance imaging-derived muscle fat content analyses.

Results: In the control group, bed rest increased the cumulative [1-(13)C]oleate and [d(31)]palmitate appearance in triglycerides (37%, P = 0.009, and 34%, P = 0.016, respectively) and nonesterified fatty acids (NEFAs) (37%, P = 0.038, and 38%, P = 0.002) and decreased muscle lipoprotein lipase (P = 0.043) and fatty acid translocase CD36 (P = 0.043) mRNA expressions. Plasma NEFA-to-triglyceride ratios for [1-(13)C]oleate and [d(31)]palmitate remained unchanged, suggesting that the same proportion of tracers enters the peripheral tissues after bed rest. Bed rest did not affect [1-(13)C]oleate oxidation but decreased [d(31)]palmitate oxidation by -8.2 +/- 4.9% (P < 0.0001). Despite a decreased spontaneous energy intake and a reduction of 1.9 +/- 0.3 kg (P = 0.001) in fat mass, exercise training did not mitigate these alterations but partially maintained fat-free mass, insulin sensitivity, and total lipid oxidation in fasting and fed states. In both groups, muscle fat content increased by 2.7% after bed rest and negatively correlated with the reduction in [d(31)]palmitate oxidation (r(2) = 0.48, P = 0.003).

Conclusions: While saturated and monounsaturated fats have similar plasma trafficking and clearance, physical inactivity affects the partitioning of saturated fats toward storage, likely leading to an accumulation of palmitate in muscle fat.

Figures

FIG. 1.

Overview of the protocols conducted during the study.

FIG. 2.

Time course of NEFAs, triglycerides (TG), insulin, and glucose concentrations (μmol/l) in the control (n = 8) and exercise (n = 8) groups 15 days before bed rest (BR) and after 32 days of bed rest. Time 0 corresponds to the standard breakfast ingestion. The postprandial cumulative responses of these parameters were calculated by the area under the curve (AUC) over 10 h postdose. Data are means ± SE. ▪, ambulatory period; •, control group; ▾, exercise group; □, bed rest period; ○, control group; ▿, exercise group.

FIG. 3.

Time course of the ratio between carbohydrate and fat oxidations (g/g) in the control (n = 8) and exercise (n = 8) groups 15 days before bed rest (BR) and after 32 days of bed rest. Time 0 corresponds to the standard breakfast ingestion. The ratio of the postprandial cumulative carbohydrate to cumulative fat oxidation were calculated by the area under the curve (AUC) over 10 h postdose. Data are means ± SE. ▪, ambulatory period; •, control group; ▾, exercise group; □, bed rest period; ○, control group; ▿, exercise group.

FIG. 4.

Time course of labeled dietary [1-13C]oleate and [d31]palmitate in triglycerides (TG) and NEFAs in the control (n = 8) and exercise (n = 8) groups 15 days before bed rest (BR) and after 32 days of bed rest. Time 0 corresponds to the standard breakfast ingestion. The cumulative responses of these parameters were calculated by the area under the curve over 10 h postdose. Data are means ± SE. ▪, ambulatory period; •, control group; ▾, exercise group; □, bed rest period; ○, control group; ▿, exercise group.

FIG. 5.

Hourly instantaneous percent recovery of [1-13C]oleate and [d31]palmitate in the control (n = 8) and exercise (n = 8) groups 15 days before bed rest (BR) and after 32 days of bed rest. Time 0 corresponds to the standard breakfast ingestion. Recoveries of [1-13C]oleic and [d31]palmitic acids were calculated as the instantaneous recovery of 13C in expired CO2 hourly sampled over the 12 h of the test and as the cumulative recovery of 2H in total body water hourly sampled through urine, respectively. Both of these recoveries are expressed as a percentage of the dose. The cumulative percent recoveries of [1-13C]oleate and [d31]palmitate were calculated by the area under the curve over the 12 h postdose and then normalized by kilograms of FFM. Data are means ± SE. ▪, ambulatory period; •, control group; ▾, exercise group; □, bed rest period; ○, control group; ▿, exercise group.

FIG. 6.

Bed rest–induced changes in expression of skeletal muscle LPL, fatty acid transporter CD36 (FAT/CD36), CPT1, acetyl-CoA dehydrogenase, GPD1, and COX4 mRNAs measured between 8 days before bed rest and after 59 days of bed rest and expressed in percentage of fold change in the control (n = 5) and exercise (n = 5) groups. Data are means ± SE. ▪, control group; □, exercise group. *P < 0.05 vs. ambulatory period. Group effect: NS.

FIG. 7.

Changes in the gastrosoleus muscular fat content during bed rest (BR) from ambulatory period (top). Regression analysis between bed rest–induced changes in cumulative [d31]palmitate (bottom) percentage recoveries (% dose) and the gastrosoleus muscle fat content after 1 month of bed rest. Muscle fat content was measured before bed rest and after 1 and 2 months of bed rest by magnetic resonance T1 signal intensity (arbitrary units) in the control (n = 8) and exercise (n = 8) groups. Bed rest induced a significant increase in muscle fat content in both groups (P = 0.051). After 1 month of bed rest, T1 signal adjusted for baseline values negatively correlated with the reduction in palmitate (y = −0.11 × +18.13) (r2 = 0.48, P = 0.003). Data are means ± SE. ○, control group; •, exercise group.