Fig 2: OXGR1 is required for metabolic beneficial effects of resistance exercise ABody weight gain in male WT littermates and OXGR1KO mice. At 8 weeks of age, male C57BL/6 WT control or OXGR1KO mice were switched to HFD. After 12 weeks of HFD feeding, mice were further divided into two groups receiving non-exercise or resistance exercise for 14 days (n = 8 per group).BExercise-induced body weight loss in male WT littermates and OXGR1KO mice. Body weights from exercise mice were subtracted by the average body weight of the non-exercise control group for each genotype (n = 8 per group).CExercise-induced fat mass loss in male WT littermates and OXGR1KO mice. Fat mass from exercise mice was subtracted by the average fat mass of the non-exercise control group for each genotype (n = 8 per group).DCumulative food intake of male WT littermates and OXGR1KO mice after 14-day resistance exercise (n = 8 per group).E, FWeight index of gWAT (E) and iWAT (F) of male OXGR1KO mice after 14-day resistance exercise (n = 8 per group).GBody composition of male OXGR1KO mice after 14-day resistance exercise (n = 8 per group).HSerum AKG levels of male WT and OXGR1KO mice after resistance exercise. Male WT and OXGR1KO mice (10 weeks old) fed with normal chow were receiving resistance exercise for 40 min (n = 8 per group). The serum AKG levels were tested before and immediately after exercise.ISerum E level in male OXGR1KO mice after 14-day resistance exercise (n = 8 per group).J–LThe mRNA expression (J) and protein expression of UCP1 (K) in the BAT or the mRNA expression of HSL and ATGL (L) in the gWAT of male OXGR1KO mice after 14-day resistance exercise (n = 4 per group).M–POxygen consumption (M, N) and RER (O, P) in male OXGR1KO mice after 14-day resistance exercise (n = 8 per group).Data information: Results are presented as mean ± SEM. In (A–D) *P = 0.05 and **P = 0.01 by two-way ANOVA followed by post hoc Bonferroni tests. In (E–L, N and P), different letters between bars indicate P = 0.05 by one-way ANOVA followed by post hoc Tukey's tests.

Fig 3: OXGR1 expressed by adrenal gland mediates the stimulatory effects of AKG on thermogenesis and lipolysis A, BBody weight gain (A) and cumulative food intake (B) of male OXGR1 adrenal-specific reexpression mice (OXGR1REAG). Male OXGR1KO mice (8 weeks old) were adrenal-specifically injected with control HBAAV2/9-GFP (OXGR1KO control) or HBAAV2/9-OXGR1 (OXGR1REAG). Two weeks after injections, mice were switched to HFD and further divided into two groups receiving tap water or water supplemented with 2% AKG for 12 weeks (n = 8 per group).C, DRepresentative image of body composition (C) and fat and lean mass index (D) of male OXGR1REAG mice treated with AKG for 12 weeks (n = 8 per group).E, FWeight index of gWAT (E) and iWAT (F) in male OXGR1REAG mice treated with AKG for 12 weeks (n = 8 per group).G, HImmunoblots (G) and quantification (H) of p-HSL and ATGL protein in gWAT of male OXGR1REAG mice treated with AKG for 12 weeks (n = 8 per group).I–LOxygen consumption (I–J) and RER (K–L) of male OXGR1REAG mice treated with AKG for 12 weeks (n = 8 per group).Data information: Results are presented as mean ± SEM. In (A, B), *P = 0.05 by two-way ANOVA followed by post hoc Bonferroni tests. In (D–F, H, J and L), different letters between bars indicate P = 0.05 by one-way ANOVA followed by post hoc Tukey's tests.