(A, B) High-fat diet (HFD) leads to exaggerated adiposity in Nr1d1Flox2-6:AdipoqCre mice. Body weight track of Cre-ve and Cre+ve male mice on HFD (solid line) or normal chow (NC) (dashed line) (A) (ap<0.05: Cre+ve NC vs. HFD; bp<0.05, Cre-ve NC vs. HFD; cp<0.05, Cre+ve HFD vs. Cre-ve HFD); total body, fat, and lean weight after 16 weeks in the high-fat diet group (B). (C, D) On histological examination of gonadal white adipose tissue (gWAT), HFD-fed Cre+ve mice display less fibrosis and inflammation than Cre-ve littermates. Representative Picrosirius Red and F4/80 immunohistochemistry images (20× magnification) (C), quantification of staining across groups, each data point represents the mean value for each individual animal (D). (E, F) Despite increased adiposity, HFD-fed Cre+ve mice display greater insulin sensitivity than Cre-ve controls. Terminal blood glucose and insulin levels (animals culled 2 hr after food withdrawal) in NC and HFD-fed in Nr1d1Flox2-6:AdipoqCre Cre-ve (black) and Cre-ve (orange) mice (E). Blood glucose values for individual animals and area under curve (change from baseline) for 16-week HFD-fed Nr1d1Flox2-6:AdipoqCre Cre-ve and Cre-ve mice undergoing insulin tolerance testing (ITT) (F). Data presented as mean ± SEM (A) or as individual data points with mean (B, D, E, F). *p<0.05, **p<0.01, two-way repeated-measures ANOVA with Tukey’s multiple comparisons tests (A), two-way ANOVA with Sidak’s multiple comparisons tests (D, E), unpaired two-tailed t-test (B, F). n=4–11/group for all panels. Picrosirius Red images for each animal available in Figure 4—source data 1.