Fig. 6: Metabolic state-dependent regulation of energy expenditure and body temperature by L-LEN–GPR50 signaling.

a, Metabolic recording of WT and Gpr50-KO mice during fasting, with saline or L-LEN injected. b, Oxygen consumption in WT mice before and after i.c.v. injection of saline or 5 nmol of L-LEN. Left, representative recording for all time periods (n = 5 and 5 mice for saline (S) and L-LEN (LL), respectively), with the gray rectangle indicating fasting and the arrows indicating drug administration. Middle, average oxygen consumption of all mice after the third injection of drug (shaded region, n = 12 and 15 mice for saline and L-LEN, respectively). Right, quantification of average oxygen consumption 2–3 h after the third injection (P = 0.0061). c, Same as b except the experiments were performed with Gpr50-KO (KO) mice (n = 6 and 6 mice for saline and L-LEN in representative experiments, respectively; n = 10 and 9 mice for saline and L-LEN in quantification, respectively; P = 0.71). d, Measurement of body temperature in WT and Gpr50-KO mice. e,f, Similar to b and c except the body temperature of different mice was measured and quantified (WT: n = 4 and 4 mice for saline and L-LEN in representative experiments, respectively; n = 7 and 7 mice for saline and L-LEN in quantification, respectively; P = 0.03; Gpr50-KO: n = 3 and 3 mice for saline and L-LEN in representative experiments, respectively; n = 6 and 6 mice for saline and L-LEN in quantification, respectively; P = 0.73). g, Blood hormone detection in fasted mice injected with saline or L-LEN. h, Blood hormone levels in fasted WT and Gpr50-KO mice after i.c.v. injection of saline or L-LEN (TSH: n = 9 and 11 mice for saline and L-LEN, respectively, in WT; P = 0.035; n = 5 and 6 mice for saline and L-LEN, respectively, in Gpr50-KO; P = 0.60; free T4: n = 6 and 7 mice for saline and L-LEN, respectively, in WT; P = 0.021; n = 11 and 12 mice for saline and L-LEN, respectively, in Gpr50-KO; P = 0.38; free T3: n = 6 and 8 mice for saline and L-LEN, respectively, in WT mice; P = 0.32; n = 11 and 13 mice for saline and L-LEN, respectively, in Gpr50-KO; P = 0.89). i, Detection of UCP1 and norepinephrine (NE) in brown adipose tissue (iBAT) of fasted mice. j, Representative blotting (left) and quantification (right) of UCP1 expression in brown adipose tissue of fasted WT or Gpr50-KO mice after saline or L-LEN injection (n = 3 and 4 mice for saline and L-LEN, respectively, in WT; P = 0.042; n = 3 and 3 mice for saline and L-LEN, respectively, in Gpr50-KO; P = 0.68). k, Quantification of norepinephrine levels in brown adipose tissue in different groups (n = 8 and 11 mice for saline and L-LEN, respectively, in WT mice; P = 0.088; n = 7 and 6 mice for saline and L-LEN, respectively, in Gpr50-KO mice; P = 0.94). Data are shown as mean ± s.e.m.; *P< 0.05 and **P < 0.01. See Supplementary Table 1 for statistics.

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