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

Abstract

27Dietary patterns are well known to contribute to the metabolic syndrome and related disorders. We 28 evaluated the impact of a short-term Westernized diet (WD) exposure on systemic plasma metabolomic 29 changes in a cohort of adult male baboons. In this pilot study, five male baboons (n=5) raised and 30 maintained on a standard monkey chow diet (high complex carbohydrates, low fat) were exposed to a 31 challenge WD (high in saturated fats and simple carbohydrates) for 7 weeks (49 d), followed by a 57-32 day washout period on monkey chow (106 d). In addition to monitoring clinical measures, we used a 33 comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (2D GC-ToF-34 MS) platform to assess the metabolomic changes in plasma at three time points. Twenty-three 35 metabolites were changed in response to the WD (49 d), but the response across the animals was highly 36 variable. All animals presented a very different metabolic profile than at baseline (0 d), and the washout 37 period resulted in a relatively homogenous metabolic state across all animals. A short-term exposure to a 38 WD led to long-term changes in the metabolic profile, suggesting a "reset" of the metabolic program. 39 40 41 42 43 44 45 46 47 48 65consume a diet high in saturated fats also tend to consume higher amounts of simple carbohydrates, and 66 this combination has been termed a Western diet (WD). A higher Western dietary pattern score is 67 associated with an increased risk for type 2 diabetes, coronary heart disease, and colon cancer [4][5][6][7][8] . 68While dietary saturated fats and simple carbohydrates separately negatively impact cardiometabolic 69 health, these two dietary elements consumed together likely act synergistically to increase both the rate 70 of disease progression as well as its severity. 71Long-term changes in body weight correlate with characteristic changes in serum metabolite 72 concentrations [9]. Changes in plasma triglyceride, cholesterol, and glucose levels are often clinical 4 73 manifestations of weight gain in response to a WD. Interestingly, improved nutrition, dieting and weight 74 loss do not invariably lead to a return to normal plasma metabolite concentrations, and these altered 75 plasma levels of specific metabolites may be contributing to the increased cardiovascular disease risk 76 observed in patients with repeated cycles of weight gain and loss (often termed yoyo dieting or weight 77 cycling) in both females [10, 11] and males [12]. However, the exact pattern of metabolic changes 78 during this weight cycling has not been characterized, and it is unknown how quickly a WD exposure 79 (with or without weight gain and subsequent loss) causes long-term changes. 80With the advent of modern metabolomics technologies, such as gas chromatography-coupled 81 mass spectrometry, it is now possible to conduct comprehensive and unbiased analyses of serum 82 samples to characterize the complex metabolic changes resulting from weight gain and changes in diet 83 patterns. In a recent stu...

Crossbred Sows Fed a Western Diet during Pre-Gestation, Gestation, Lactation, and Post-Lactation Periods Develop Signs of Lean Metabolic Syndrome That Are Partially Attenuated by Spirulina Supplementation

“…Chronic excessive intake of dietary saturated fat, sugars, and cholesterol may lead to an alteration in the activity of transcription factors that results in a dysregulation of gene expression favoring intra-organ lipid accumulation and, in the long term, other metabolic disturbances [2][3][4]. Even before the onset of the metabolic syndrome, including visible changes in body weight (BW) and body composition, shifts in metabolic and inflammatory blood parameters point towards an unfavorable metabolic state, as observed in rodents and primates [5][6][7].…”