Fig. 1: HFD-induced anxiety and depression correlate with the desensitization of AgRP neurons.

a Representative activity tracers in OFT by WT mice fed with chow and 6 week of HFD. b Time spent in the center zone of the open field. c Entries of entering the center zone of the open field by mice fed with chow and HFD for 6 week. d Representative activity tracers in EPM in WT mice fed with chow and 6 week of and HFD. e Time spent in the open arm. f Entries of mice entered the open arm. Error bars represent mean ± SEM. n = 9–12 per group; *p < 0.05, LFD vs HFD at week 5 and 6, two-way ANOVA and followed by Bonferroni comparisons test. g Representative in vivo fluorescence traces of AgRP neurons in Agrp^Cre mice with injection of AAV9-FLEX-GCaMP6f into the ARC after chronic treatment of HFD or low-fat diet (LFD) under fed ad-lib or fasted condition. h Heat map of color-coded changes of fluorescence intensity in mice as described in (g). i The numbers of fluorescence transients detected in AgRP neurons in mice as described in (g). Error bars represent mean ± SEM. n = 10 per group; *p < 0.05, LFD vs LFD + Fasting; ^#p < 0.05, LFD vs HFD; ^‡p > 0.05, HFD vs HFD + Fasting; one-way ANOVA and followed by Tukey comparisons test. j Representative physical activity tracers (left) and heating maps of real-time AgRP neuronal activities (right) in OFT test in Agrp^Cre mice injected with AAV9-FLEX-GCaMP6f into the ARC followed with a chronic treatment of HFD or LFD under well-fed condition. Gray bars denote when the mice were within the center zone. k Representative in vivo fluorescence traces of AgRP neurons during OFT behavior test. l The number of fluorescence transients detected in AgRP neurons. m Correlation between the probability of AgRP neurons firing and the duration of the LFD-treated mice in the center zone of OFT. n Correlation between the probability of AgRP neurons firing and the duration of HFD-treated mice in the center zone of OFT. o Representative activity tracers (left) and heating maps (right) in EPM test in Agrp^Cre mice injected with AAV9-FLEX-GCaMP6f into the ARC followed with a chronic treatment of HFD or control low-fat diet (LFD) under well-fed and fasting condition. Gray bars denote when the mice were in the open arm. p Examples of in vivo fluorescence changes of AgRP neurons during EPM behavior test. q The number of fluorescence transients detected in AgRP neurons. r Correlation between the probability of AgRP neurons firing and the duration of the LFD fed mice in the open arm of EPM. s Correlation between the probability of AgRP neurons firing and the duration of HFD-fed mice in the open arm of EPM. Error bars represent mean ± SEM. n = 10 per group; *p < 0.05, one-way ANOVA and followed by Tukey comparisons test.