(OR34-04-24) Metabolic Flexibility in Response to a High-Fat Meal Challenge Is Not a Universal Indicator of Overall Metabolic Health

Objectives: Metabolic flexibility, the ability to switch fuel sources based on availability, is a generally accepted sign of metabolic health, and is impaired in people with insulin resistance. The Dietary Guidelines for Americans (DGA) suggests a low fat, high fiber diet to improve metabolic health. Here we evaluate the effect of DGA based diet on metabolic flexibility and health in women with insulin resistance.

Methods: In an 8-week controlled feeding intervention, overweight/obese women with ≥1 metabolic syndrome characteristics were randomized to consume either a diet based on DGA 2010 (DGA) or a ‘Typical’ American Diet (TAD), n = 22 each. Participants were given a high-fat meal challenge (HFMC-60% fat, 25% carbs, and 15% protein) at weeks 0, 2, and 8, when circulating lipids, substrate oxidation, plasma metabolome and lipidome were measured at 0, 0.5, 3 and 6h time points. Metabolic flexibility was evaluated as the change in fat oxidation over time. Mixed model analyses and multivariate approaches were used to evaluate the effect of diet on these outcomes; p< 0.05 was considered statistically significant.

Results: Total cholesterol and HDLc were lower at wk8 compared to wk0, but only in DGA, at wk8 groups were not different. Metabolic flexibility was not affected by diet. Consistent (all weeks) fat burner phenotypes based on % of ingested fat (HFMC) burned were observed. High burners (HB) burned >40% of ingested fat vs low burners burned < 30% (LB). HB group had higher fat mass, total mass, lean mass, BMI and lower HDLc. Partial least squares discriminant analysis (Q2: 0.20, R²X: 0.177, R²Y: 0.716) identified, among others, that LB, but not HB, were associated with higher rates of disappearance of acylcarnitines from plasma.

Conclusions: An 8-week DGA based diet did not improve conventional measures of plasma lipids or metabolic flexibility. The HB group, which demonstrated consistent fuel switching to fat following fat intake, did not display metabolically optimal lipid profile or anthropometry. Further, plasma acylcarnitines, a sign of metabolic disorders when high, cleared faster in LB, and not in HB. Overall, in this group of women with insulin resistance, being able to switch to burn fat in response to a fat bolus did not offer additional metabolic health benefits.

Funding Sources: National Dairy Council, Campbell Soup Co., USDA- ARS, West Coast Metabolomics NIH Pilot Award