Metabolic Reprogramming: Short-term Western Diet Exposure Induces Sustained Changes in Plasma Metabolites

Abstract Dietary patterns are well known to contribute to the metabolic syndrome and related disorders. We evaluated the impact of a short-term Westernized diet (WD) exposure on systemic plasma metabolomic changes in a cohort of adult male baboons. In this pilot study, five male baboons (n=5) raised and maintained on a standard monkey chow diet (high complex carbohydrates, low fat) were exposed to a challenge WD (high in saturated fats and simple carbohydrates) for 7 weeks (49 d), followed by a 57-day washout period on monkey chow (106 d). In addition to monitoring clinical measures, we used a comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (2D GC-ToF-MS) platform to assess the metabolomic changes in plasma at three time points. Twenty-three metabolites were changed in response to the WD (49 d), but the response across the animals was highly variable. All animals presented a very different metabolic profile than at baseline (0 d), and the washout period resulted in a relatively homogenous metabolic state across all animals. A short-term exposure to a WD led to long-term changes in the metabolic profile, suggesting a “reset” of the metabolic program.