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Multiple studies have shown throughout the past 10+ years that grain sorghum (GS) lipid extract protects against high plasma and hepatic cholesterol and, to a lesser degree, positively modulate the gut microbiota in response to a high fat (HF) diet. However, the impact of GS lipids on intestinal stress induced by such a diet remains largely unknown. The objective of this project was to determine the ability of GS crude lipid (GS-CL) obtained from the surface of GS whole kernel to protect energy metabolism and short chain fatty acid (SCFA) profile produced by the gut microbiome that may be negatively affected by a HF diet. If left unchecked, such impacts can lead to hypoxia or inflammation and thereby other chronic conditions. In our study, male hamsters were fed with either a low fat control diet, a HF diet or a HF diet supplemented with 1, 3, 5% (w/w) GS-CL for four weeks. The hamsters were then euthanized and the large intestine obtained and analyzed using targeted metabolomics. Analysis of central carbon metabolites showed that the HF diet impaired energy generation and disrupted cellular redox balance. A significant increase of many intermediates of glycolysis (particularly glyceraldehyde-3-phosphate, glycerate-3-phosphate and phosphoenolpyruvate) and tricarboxylic acid (TCA) cycle (particularly succinate, fumarate and malate) occurred in response to a HF influence, while nearly all amino acids were significantly lower compared to the low fat diet. The GS-CL supplements were able to maintain energy levels in the large intestine, especially the 1 and 3% but were not able to rebalance redox equilibrium completely. Moreover, multivariant analysis including orthogonal-partial least squares-discrimination analysis (OPLS-DA) demonstrated that the GS-CL supplements were able to gradually maintain the HF affected metabolites to levels trending or comparable to the control level, with 3% supplement being the optimal diet in this regard. In general, the data indicated that the GS-CL supplements slowed down the gluconeogenesis and anaplerosis from pyruvate and amino acids, which in turn mitigated the accumulation of glycolysis and TCA intermediates in a dose-depended manner. In addition, the GS-CL supplements positively affected the short chain fatty acid (SCFA) produced by large intestine microbiome, with the 3% diet again exerting the optimal protection, against HF induced changes in SCFA profile followed by 1% supplement. Synergistic interaction among various components in GS-CL (such as the characterized phytosterols and policosanols) may be responsible for some of the metabolic responses as the effects of GS-CL is optimal compared to that reported of the GS oil or wax fraction alone. This study is the first to provide whole-scale impact of GS-CL on cellular energy and central carbon metabolism using a combined approach of metabolomics and multivariant analysis, which effectively demonstrate the potentials of GS-CL as a supplement to prevent or contain chronic metabolic diseases.
Advisor: Vicki Schlegel