Extended Data Fig. 5: LCA ameliorates age-related insulin resistance without decreasing glucose production.
From: Lithocholic acid phenocopies anti-ageing effects of calorie restriction
a-c, LCA ameliorates age-associated insulin resistance in mice. Ad libitum-fed, aged male mice were fed with (2-hydroxypropyl)-β-cyclodextrin-coated LCA at 1 g/l in drinking water for 1 month, followed by ipGTT (a, results of blood glucose and area under the curve (AUC) are shown as mean ± s.e.m. on the left panel; n = 5 (vehicle) or 6 (LCA) mice for each condition, and P value by two-way repeated-measures (RM) ANOVA followed by Sidak’s test (blood glucose), or by two-sided Student’s t-test (AUC); and the serum insulin levels during ipGTT are shown on the right panel, results are mean ± s.e.m.; n = 4 mice and P value by two-way RM ANOVA followed by Sidak’s test), ITT (b, results of blood glucose and AUC are shown as mean ± s.e.m.; n = 5 (vehicle) or 6 (LCA) mice for each condition, and P value by two-way RM ANOVA followed by Sidak’s test (blood glucose), or two-sided Student’s t-test (AUC)), and the hyperinsulinaemia euglycaemic clamp (c, the blood glucose levels and the GIR values during the clamp are shown on the left panel as mean ± s.e.m.; n = 10 mice; P value by two-way RM ANOVA followed by Sidak’s test; and the glucose disposal rates and the HGP rates, calculated according to the average values of GIR during the steady-state (90–120 min, indicated by a dashed line), on the right panel as mean ± s.e.m.; P value by two-sided Student’s t-test). d-k, LCA ameliorates insulin resistance in aged mice without decreasing glucose production. Mice were treated as in a, followed by an 8 h-fasting period (except for liver glycogen, in which both fed and fasting mice were used). The carbon sources responsible for glucose production, including serum β-hydroxybutyrate (d), serum free fatty acids (e), serum glycerol (f), muscle glycogen (g), liver glycogen (h), muscle (i) and liver triglyceride (j), along with serum glucagon (k), were determined. Results are mean ± s.e.m.; n = 4 (d, vehicle groups of e and g, feeding group of h, and vehicle group of k) or 5 (others) mice for each treatment, and P value by two-way ANOVA followed by Tukey’s test (h), or by two-sided Student’s t-test (others). Experiments in this figure were performed three times.
