Fighting Fire with Fire: Impact of Sugary Diets on Metabolically Deranged Mice

Background/Objectives: There is controversy about the health risks of sugary diets. A recent study reported that chronic consumption of 11% sugar solutions improved glycemic control in lean mice. Based on this finding, we hypothesized that chronic consumption of the same 11% sugar solutions would also improve glycemic control in metabolically deranged mice. Methods: We exposed mice to a high-fat/high-sugar diet for 12 weeks. Then, we switched the mice to a control (i.e., standard chow) or one of four experimental diets for 8 weeks. The experimental diets contained standard chow plus an 11% solution of glucose or high-fructose syrup. The sugar syrups were derived from corn or cellulose. We included the cellulosic syrups because they contain polyphenols, which are thought to promote glycemic control. We measured body weight, adiposity, glucose tolerance, insulinemia, insulin sensitivity, body composition, and avidity for sweeteners. Results: Mice switched to the control diet lost weight, whereas mice switched to the experimental diets remained obese and hyperinsulinemic. Thus, the experimental diets did not cause the mice to regain normal metabolic health. Nevertheless, we observed (i) improvements in glucose tolerance in mice on both the control and experimental diets; (ii) reduced insulinemia and enhanced insulin sensitivity in mice offered the cellulosic syrups; (iii) elevations in cephalic-phase insulin responses in mice on the experimental diets; and (iv) increased avidity for sweeteners in mice on the control but not the experimental diets. Conclusions: Switching metabolically deranged mice to the experimental diets, particularly those with cellulosic sugars, improved glucose tolerance and insulin sensitivity.