Fructose

Fructose (99% purity), tetramethylammonium chloride ([N₁₁₁₁]Cl, purity 98%) and DL-Lactic Acid (LA, 85% purity) were purchased from Acros Organics (Belgium). 5-Hydroxymethylfurfural (5-HMF, purity ≥ 99%), cholinium chloride ([Ch]Cl, ≥99% purity), levulinic acid (Lev, purity 98%), glycolic acid (GA, purity 99%) and γ-valerolactone (GVL, 98% purity) were supplied by Sigma Aldrich (USA). Citric acid mono hydrate (CA, purity ≥ 99.5%) and DL-malic acid (MA, purity 99.5%) were purchased from Panreac (Spain). Cholinium bromide ([Ch]Br, purity ≥ 98%) was purchased from TCI (Japan) and cholinium acetate ([Ch]Ac, purity 98%) was purchased from Iolitec (Germany).

This study was approved by the Institutional Animal Care and Use Committee of the University of Massachusetts Medical School. Principles of laboratory animal care were followed. The experimental time line and setup of mouse feeding on chow diet and our novel high fat, high cholesterol, high sugar diet (HF–HC–HSD) is outlined in Additional file 1: Figure 1S. Male C57Bl/6 wild-type mice that were 8–10 weeks old (n = 6–12 per group) (Jackson Laboratory, Bar Harbor, ME, USA) were fed either a control chow diet or a Western diet equivalent high-fat, high-carbohydrate diet [Surwit diet (58% kcal 35 g% fat)] supplemented with 10% cholesterol (Research Diets, New Brunswick, NJ, USA); with drinking water supplemented with a high-fructose corn syrup equivalent consisting of a total of 42 g/L of carbohydrates at a ratio of 55% fructose (Acros Organics, Morris Plains, NJ, USA) and 45% sucrose (Sigma-Aldrich, St. Louis, MO, USA) by weight, partially based on the study by Kohli et al. [19 (link)]. The mice were given ad libitum access to the food and water for 8, 27 or 49 weeks. See Additional File 1: Figure 2S for diet details.

Aytex^® P wheat starch, an unmodified, highly purified native wheat starch (<0.2% protein, <0.1% fat, <0.2% ash, 9.9% water, and 25% amylose) [42 ] was donated by ADM (Minneapolis, MN, USA) and used “as is”. Twenty different sugars and sugar alcohols that may be found in food products and/or have stereochemical structures of interest were used: xylose, ribose, glucose, galactose, fructose, mannose, and mannitol from Acros Organics (Fair Lawn, NJ, USA); L-sorbose and xylitol from Sigma-Aldrich (St. Louis, MO, USA); trehalose dihydrate from Hayashibara Company (Okayama, JP, USA); tagatose and allulose from Sensato (Albany, NY, USA); maltose monohydrate and lactose monohydrate from Fisher Chemical (Fair Lawn, NJ, USA); isomaltulose monohydrate and isomalt ST (~1:1 ratio of glucopyranosyl sorbitol and glucopyranosyl mannitol dihydrate [43 ]) from BENEO-Palatinit Gmbh (Mannheim, DE, USA); sorbitol from Amresco (Solon, OH, USA); sucrose from Mallinckrodt Chemicals (Phillipsburg, NJ, USA); and maltitol and raffinose pentahydrate from Alfa Aesar (Ward Hill, MA, USA) (Table 1). Calcium propionate was from Sigma-Aldrich. The water used in this study was processed using reverse osmosis, then filtered by a Barnstead E-Pure Lab Water System (Dubuque, IA, USA) to >17.4 milliohm-cm.