Physical Inactivity Differentially Alters Dietary Oleate and Palmitate Trafficking

Abstract

1OBJECTIVE-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 ϭ 8) and the effect of concomitant resistance/aerobic exercise training as a countermeasure (exercise group, n ϭ 8). Trafficking of stable isotope-labeled dietary fats was combined with muscle gene expression and magnetic resonance imaging-derived muscle fat content analyses. 31 ]palmitate oxidation by Ϫ8.2 Ϯ 4.9% (P Ͻ 0.0001). Despite a decreased spontaneous energy intake and a reduction of 1.9 Ϯ 0.3 kg (P ϭ 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 ϭ 0.48, P ϭ 0.003). I n our search of the environmental factors that fuelled the pandemic of obesity, we face a paradox. Although sedentary lifestyle has been highlighted for decades as one of the main factors triggering weight gain, the physiology of physical inactivity has received little attention (1). Clearly, the causal relationships between sedentary behaviors and obesity are essentially based on epidemiological studies or on the indirect beneficial effects of exercise training (2). None of these studies provide evidence to support a cause-and-effect relationship. RESULTS-In CONCLUSIONS-WhileObesity is a fat storage disease characterized by insulin resistance and a decreased capacity to oxidize lipids (3) in fasting (4) and postprandial (5) conditions. Because weight reduction was not associated with improvement in fat utilization (6), it was suggested as a primary impairment in the etiology of obesity, rather than an adaptive response. Consequently, the delineation of the causes responsible for this reduced capacity to oxidize fat appears to be a fundamental prerequisite to develop efficient strategies against obesity.We previously extended the early Mayer hypothesis (7) and hypothesized that the decreased fat oxidation observed in obese and postobese subjects is due to the generalized adoption of sedentary behaviors (8). Using strict bed rest as a model, we showed that physical inactivity, per se (i.e., independent of the known physical inactivity-induced energy balance changes), lowers fasting and postprandial fat oxidation (9). Unexpectedly, whereas monounsaturated dietary fat (oleate) oxidation remained unaffected by bed rest, saturated fat (palmitate) oxidation decreased by 11% (9). These results are interesting when considering the north/south gradient in obesity prevalence in France that was not associated with the overall energy intake but in the greater amount of saturated fat in the diet (10).The main objective of our present study wa...

Impact of insulin deprivation and treatment on sphingolipid distribution in different muscle subcellular compartments of streptozotocin-diabetic C57Bl/6 mice

“…Until now, most studies have focused on palmitate and its involvement in intramuscular ceramide accumulation and induction of insulin resistance (1,19,53,64), the rationale being that it can form both the sphingoid backbone (dhSph, through condensation of palmitoyl-CoA and L-serine by sarcoplasmic SPT) and palmitoyl-ceramide (through the activity of sarcoplasmic ceramide synthase), thus increasing ceramide content by two parallel mechanisms. Palmitate, but not oleate, was shown to increase ceramide accumulation in muscle myotubes (11), decrease phosphorylation of Akt (55), and induce muscle insulin resistance (52), the latter even improving palmitate-induced insulin resistance (6,14,55). On the contrary, a study by Thompson et al (69) reported that oleate and linoleate were more potent inhibitors of insulin-stimulated glucose uptake, glucose phosphorylation, and glycogen synthesis in isolated soleus muscle than palmitate.…”

Synthesis and Preliminary Evaluation of 18-18F-Fluoro-4-Thia-Oleate as a PET Probe of Fatty Acid Oxidation

“…Although oleate and palmitate have been shown to be similarly taken up and oxidized in human myocardium (18), their use in the whole body and skeletal muscle in humans has shown some notable differences (19)(20)(21)(22). Because dietary oleate (18:1) is preferentially oxidized relative to palmitate (16:0) and stearate (18:0) (22), we anticipated that an oleic acid analog of 18 F-FTP might show a higher specificity for mitochondrial FAO than 18 F-FTP itself.…”

Measuring plasma fatty acid oxidation with intravenous bolus injection of 3H- and 14C-fatty acid

“…One-way ANOVA was also used to compare the model parameters, which were k (rate constant) and maximum percent recovery of [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]acetate among the three conditions. A repeated-measures ANOVA was used to compare [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]palmitate versus [9, H] palmitate oxidation time courses within each condition.…”

“…A repeated-measures ANOVA was used to compare [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]palmitate versus [9, H] palmitate oxidation time courses within each condition. Tukey post hoc test was used to locate signifi cant differences.…”

“…Impaired plasma FFA oxidation occurs in disease states such as type 2 diabetes (T2DM) ( 1, 2 ). Therefore, accurate measures of FFA oxidation are important to help understand the pathophysiology of T2DM and related diseases.Numerous investigators have used carbon and hydrogen isotope-labeled FA tracers to measure FA oxidation by means of continuous intravenous infusions ( 3-10 ) and dietary ingestion of the tracers (11)(12)(13)(14). Rapid intravenous injection of an FFA tracer is useful when aspects of nonoxidative FA metabolism are investigated.…”