Fermentable Non-Digestible Dietary Fiber and Bioactive Compounds Affect Aging and Fat Deposition in Caenorhabditis elegans

Abstract

Overweight and obesity have been imposing $147 billion a year to the health care system in the United States. Limited medications are available in the market with side effects. Surgical treatments are second-line obesity treatments. Short chain fatty acids (SCFAs) produced from the fermentable resistant starch improves the secretion of satiety hormones peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) from L-endocrine cells of cecum and colon. We hypothesized that consumption of fermentable non-digestible dietary fiber and bioactive compounds will increase insulin sensitivity, reduce body fat, and improve healthspan in Caenorhabditis elegans (C. elegans), and hyperglycemia (2% glucose) that may cause insulin resistance and impair lipid metabolism will attenuate these effects. Wild type C. elegans N2 or sir-2.1(ok434)IV, daf-16(mgDf50)I, and daf-16(mgDf50)I;daf-2(m65)III mutants were used. The control animals were fed with E. coli OP50. Experimental groups were fed with additional treatments: butyrate (0.3mM, 0.6mM), sodium acetate (5mM, 50mM), sodium propionate (7mM), or tributyrin (0.5mM, 3mM); PWB, oats or wheat bran (0.5%, 1.0%, or 3.0% w/v) with or without additional 2% glucose. SCFAs increased the lifespan of N2 and daf-16(mgDf50)I, but reduced lifespan in the daf-16/daf-2 deficient and sir-2.1(ok434)IV mutants. PWB or wheat bran sustained the pharyngeal pumping rate (PPR) in N2, sir-2.1(ok434)IV, daf-16(mgDf50)I, and daf-16(mgDf50)I;daf-2(m65)III. The N2, daf-16, or sir-2.1 mutant increased the PPR following oat consumption. This increase persisted in the presence of glucose at a low dose in daf-16 or daf-16/daf-2 mutant. The Nile red stained intestinal fat deposition (IFD) was reduced by butyrate (0.3, 0.6mM), acetate (100mM), propionate (0.3mM), and tributyrin (0.1, 1mM) in N2; and was increased in sir-2.1 mutant. PWB reduced IFD in N2, sir-2.1 or daf-16 mutants. Hyperglycaemia attenuated the effects on IFD in N2 or daf-16/daf-2 mutant. Oat-feeding decreased IFD in N2, and daf-16 or daf-16/daf-2 mutant with or without hyperglycaemia. Wheat bran reduced IFD in N2, and in daf-16 or daf-16/daf-2 mutants without hyperglycemia, while hyperglycemia increased IFD in sir-2.1(ok434)IV. In summary, PWB, oats, wheat bran, and SCFAs reduced the IFD and improved the healthspan in C. elegans, and these effects were mediated by the sir-2.1, daf-2, or daf-2/daf-16 pathways.