Fig. 1: Leptin deficiency increases endoplasmic reticulum stress markers in the developing hypothalamus.

Relative expression of activating transcription factor 4 (Atf4), 6 (Atf6), X-box binding protein (Xbp1), glucose regulated protein GRP78 (referred to as Bip), and CCAAT-enhancer-binding protein homologous protein (Chop) mRNA a in the hypothalamus of embryonic day (E)14.5 mice (n = 4–5 per group) and b in the arcuate nucleus (ARH) of postnatal day (P) 0 wild-type (WT) and leptin-deficient (ob/ob) mice (n = 5–6 per group). c Relative expression of Atf4, Atf6, Xbp1, Bip, and Chop mRNA in the ARH of P10 WT mice and ob/ob mice treated neonatally either vehicle or tauroursodeoxycholic acid (TUDCA) or leptin (WT, ob/ob + Vehicle, ob/ob + TUDCA n = 4, ob/ob + Leptin: n = 5 per group). d Representative images and quantification of Atf4, Atf6, Xbp1, Bip, and Chop mRNA (green) in arcuate pro-opiomelanocortin (Pomc)- (white) and agouti-related peptide (Agrp) (red) mRNA-expressing cells of WT and ob/ob mice at P10 (n = 3–4 per group). e Relative expression of Atf4, Atf6, Xbp1, Bip, and Chop mRNA in the ARH of 10-week-old adult WT mice and ob/ob mice treated neonatally either vehicle or TUDCA (n = 6 per group). Relative expression of Atf4, Atf6, Xbp1, Bip, and Chop mRNA in the paraventricular nucleus (PVH) of f P0 (n = 4 per group), g P10 (n = 6 per group), and h 10-week-old adult WT mice and ob/ob mice treated neonatally either vehicle or TUDCA (n = 6 per group). i Relative expression of Atf4, Atf6, Xbp1, Bip, and Chop mRNA in hypothalamic mHypoE-N43/5 cell lysates treated with dimethyl sulfoxide (DMSO, control) or leptin (LEP, 100 ng/ml) or tunicamycin (TUN, 0.1 µg/ml) or TUN + LEP for 5 h (n = 4 per group). Error bars represent the SEM. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, and ****P ≤ 0.0001 versus ob/ob mice (d, f), *P ≤ 0.05, **P ≤ 0.01, ****P ≤ 0.0001 versus vehicle-injected ob/ob mice (c, e, g, h). **P ≤ 0.01 and ****P ≤ 0.0001 versus tunicamycin treated group (i). Statistical significance was determined using two-way ANOVA followed by Tukey’s Multiple Comparison test (a–i). Scale bar, 5 µm (d). Source data are provided as a Source Data file.