Extended Data Fig. 6: 4HPAA, 4HPP, and 3HPP target intestines to maximize anti-obesity effects.

a, Representative images of H&E-stained adipose tissues, including iBAT, iWAT, and eWAT, from ND/HFD-fed mice IP injected with saline, 4HPAA, and 3HPP for 12 weeks. b, Box and whisker plots showing the measured LDL-C and TC in HFD-fed mice IP injected with 4HPAA (n = 6), 3HPP (n = 7), or saline (n = 3). The maxima, upper quartiles, medians, lower quartiles, and minima are shown. c, The triglyceride concentrations in the 3T3L1-derived adipocytes after 4HPAA, 3HPP, or 4HPP treatment, respectively (n = 5 per group). d, The 4HPAA concentrations in the contents of the jejunum, ileum, cecum, and colon (feces), as well as in the serum of mice after a seven-day 4HPAA feeding were measured and shown. For fecal samples, n = 10 mice per group. For other samples, n = 6 (control) or n = 8 (4HPAA-fed) mice per group. e, The gray-shaded section represents the proportion of each bacterial family in the gut microbiota before treatment with small molecules, while the white-shaded section shows the change in the proportion of the specific bacterial family after one month of treatment (n = 3 for ND group, n = 6 for other groups). For b-e, error bars indicate mean ± SEM, statistical analysis was assessed by the two-tailed Mann-Whitney test. Experiments in a-d were repeated twice independently with similar results.