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...

Aims/hypothesis: We investigated the effects of rosiglitazone on NEFA and triglyceride metabolism in type 2 diabetes. Methods: In a double-blind, placebo-controlled, cross-over study of rosiglitazone in diet-treated type 2 diabetic subjects, we measured arteriovenous differences and tissue blood flow in forearm muscle and subcutaneous abdominal adipose tissue, used stable isotope techniques, and analysed gene expression. Responses to a mixed meal containing [1,1,1-13 C]tripalmitin were assessed. Results: Rosiglitazone induced insulin sensitisation without altering fasting NEFA concentrations (−6.6%, p=0.16). Postprandial NEFA concentrations were lowered by rosiglitazone compared with placebo (−21%, p=0.04). Adipose tissue NEFA release was not decreased in the fasting state by rosiglitazone treatment (+24%, p=0.17) and was associated with an increased fasting hormone-sensitive lipase rate of action (+118%, p=0.01). Postprandial triglyceride concentrations were decreased by rosiglitazone treatment (−26%, p<0.01) despite unchanged fasting concentrations. Rosiglitazone did not change concentrations of triglyceride-rich lipoprotein remnants. Adipose tissue blood flow increased with rosiglitazone (+32%, p=0.03).

Background: Prolonged postprandial hypertriglyceridemia is a potential risk factor for cardiovascular diseases. In the context of obesity, this is associated with a chronic imbalance of lipid partitioning oriented toward storage and not toward b-oxidation. Objective: We tested the hypothesis that the physical structure of fat in a meal can modify the absorption, chylomicron transport, and further metabolic handling of dietary fatty acids. Design: Nine normal-weight and 9 obese subjects were fed 40 g milk fat (+[13 C]triacylglycerols), either emulsified or nonemulsified, in breakfasts of identical composition. We measured the postprandial triacylglycerol content and size of the chylomicron-rich fraction, plasma kinetics of [ 13 C]fatty acids, exogenous lipid oxidation with breath-test/indirect calorimetry, and fecal excretion. Results: The emulsified fat resulted in earlier (.1 h) and sharper chylomicron and [13 C]fatty acid peaks in plasma than in spread fat in both groups (P , 0.0001). After 2 h, the emulsified fat resulted in greater apolipoprotein B-48 concentrations (9.7 6 0.7 compared with 7.1 6 0.9 mg/L; P , 0.05) in the normal-weight subjects than did the spread fat. In the obese subjects, emulsified fat resulted in a 3-fold greater chylomicron size (218 6 24 nm) compared with the spread fat (P , 0.05). The emulsified fat induced higher dietary fatty acid spillover in plasma and a sharper 13 CO 2 appearance, which provoked increased exogenous lipid oxidation in each group: from 45% to 52% in normal-weight subjects (P , 0.05) and from 40% to 57% in obese subjects (P , 0.01). Conclusion: This study supports a new concept of "slow vs fast fat," whereby intestinal absorption can be modulated by structuring dietary fat to modulate postprandial lipemia and lipid b-oxidation in humans with different BMIs. This trial was registered at clinicaltrials.gov as NCT01249378.Am J Clin Nutr 2013;97:23-36.

Objectives:Changes in the way dietary fat is metabolized can be considered causative in obesity. The role of sedentary behavior in this defect has not been determined. We hypothesized that physical inactivity partitions dietary fats toward storage and that a resistance exercise training program mitigates storage.Design:We used bed rest, with randomization to resistance training, as a model of physical inactivity.Setting:The trial took place at the Space Clinic (Toulouse, France).Participants:A total of 18 healthy male volunteers, of mean age ± standard deviation 32.6 ± 4.0 y and body mass index 23.6 ± 0.7 kg/m2, were enrolled.Interventions:An initial 15 d of baseline data collection were followed by 3 mo of strict bed-rest alone (control group, n = 9) or with the addition of supine resistance exercise training every 3 d (exercise group, n = 9).Outcome measures:Oxidation of labeled [d31]palmitate (the main saturated fatty acid of human diet) and [1-13C]oleate (the main monounsaturated fatty acid), body composition, net substrate use, and plasma hormones and metabolites were measured.Results:Between-group comparisons showed that exercise training did not affect oxidation of both oleate (mean difference 5.6%; 95% confidence interval [95% CI], −3.3% to 14.5%; p = 0.20) and palmitate (mean difference −0.2%; 95% CI, −4.1% to 3.6%; p = 0.89). Within-group comparisons, however, showed that inactivity changed oxidation of palmitate in the control group by −11.0% (95% CI, −19.0% to −2.9%; p = 0.01) and in the exercise group by −11.3% (95% CI, −18.4% to −4.2%; p = 0.008). In contrast, bed rest did not significantly affect oleate oxidation within groups. In the control group, the mean difference in oleate oxidation was 3.2% (95% CI, −4.2% to 10.5%; p = 0.34) and 6.8% (95% CI, −1.2% to 14.7%; p = 0.08) in the exercise group.Conclusions:Independent of changes in energy balance (intake and/or output), physical inactivity decreased the oxidation of saturated but not monounsaturated dietary fat. The effect is apparently not compensated by resistance exercise training. These results suggest that Mediterranean diets should be recommended in sedentary subjects and recumbent patients.