Fig. 4: Expression of NDI1 prevents diet-induced metabolic dysfunction in mice lacking the circadian clock in adipocytes.
From: Adipocyte NADH dehydrogenase reverses circadian and diet-induced metabolic syndrome
a, Intracellular NAD+-to-NADH ratio and OCR in the presence of the indicated substrates and inhibitors in primary white adipocytes differentiated from control, NDI1, Bmal1 KO and Bmal1 KO + NDI1 mice (n = 5). b, Body weight during HFD feeding for 12 weeks (control n = 12, Bmal1 KO n = 12, Bmal1 KO + NDI1 n = 7). c, Oral GTT and insulin during the GTT at 6 weeks of HFD feeding (control n = 12, Bmal1 KO n = 12, Bmal1 KO + NDI1 n = 7). d, Oral triglyceride (TG) clearance test at 6 weeks of HFD feeding (control n = 12, Bmal1 KO n = 12, Bmal1 KO + NDI1 n = 7). e, snRNA-seq was performed on gWAT from control (Bmal1loxP/loxP; NDI1LSL), Bmal1 KO (Adipoq-cre; Bmal1loxP/loxP) and Bmal1 KO + NDI1 (Adipoq-cre; Bmal1loxP/loxP; NDI1LSL) mice. Uniform manifold approximation and projection (UMAP) plot showing WAT adipocyte nuclei from control, Bmal1 KO and Bmal1 KO + NDI1 mice (the WAT from four mice was pooled for each sample). f, KEGG pathway analysis of downregulated genes in Bmal1 KO versus control adipocytes (top) and upregulated genes in Bmal1 KO + NDI1 versus Bmal1 KO adipocytes (bottom). g, Heatmap of differentially abundant genes (adjusted P < 0.05) in adipocyte clusters between control, Bmal1 KO and Bmal1 KO + NDI1 mice. Data are presented as the mean ± s.e.m. a–d, Statistical significance was calculated using a one-way ANOVA followed by multiple comparisons in a (left) and a two-way ANOVA followed by Dunnett’s multiple comparisons test with the Bmal1 KO set as the reference group in a (right) and b–d. The # symbol denotes statistical significance between Bmal1 KO and the indicated groups. *P < 0.05, **P < 0.01, ***P < 0.001. Panel e includes elements created in BioRender; M, B. (2025) https://BioRender.com/s27y548 (2025).
