Fig. 4: AA005 resists HFD-induced obesity in mice by targeting HADHA.

a Heatmap and histogram depicting the tissue distribution of AA005 in mice at various time points after AA005 administration (n = 3 per group). b Weight gain of male littermates fed a high-fat diet (HFD) in Hadha^fl/fl and Hadha^ΔAdipo (adipose Hadha deficiency) mice was recorded for 18 weeks (n = 6). c Representative photograph of Hadha^fl/fl and Hadha^ΔAdipo mice fed HFD at experimental endpoint. Scale bar, 1 cm. d Fat and lean mass were recorded after 18 weeks treatment (n = 5). e Fat weight of iWAT, asWAT, eWAT, rWAT, mWAT, and BAT in Hadha^fl/fl and Hadha^ΔAdipo mice fed HFD (n = 6). Glucose tolerance test (GTT) (f), and insulin tolerance test (ITT) (g) performed on Hadha^fl/fl and Hadha^ΔAdipo mice fed HFD (n = 6 for each group). h Comparison of body temperature between the two groups (n = 5 per group). Three different biological replicates were tested. Mice at the end of week 17 were performed metabolic cage assays for comparison of 24 h energy expenditure between Hadha^fl/fl and Hadha^ΔAdipo mice fed HFD (i) (n = 5 per group); The adjusted means of energy expenditure in the two groups analysed by ANCOVA. (j) (n = 5); O₂ consumption (k, l) and CO₂ production (m, n) measured during a 24 h period (k, m) (n = 5); Average values for the light and dark periods, respectively (l, n) (n = 5). o, Weight gain recorded over 20 weeks (n = 6) in male littermates fed HFD with or without AA005 treatment in Hadha^ΔAdipo mice. Glucose tolerance test (GTT) (p), area under the curve (AUC) of GTT (q), insulin tolerance test (ITT) (r), and AUC of ITT (s) performed on vehicle and AA005-treated Hadha^ΔAdipo mice (n = 6). Data are presented as mean ± SEM. Unpaired, two-tailed Student’s t test. *P < 0.05, **P < 0.01, ***P < 0.001, NS indicates not significant. Source data are provided as a Source Data file.