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. 2022 Feb 1;34(2):269–284.e9. doi: 10.1016/j.cmet.2021.12.023

Figure 5.

Figure 5

Obesity-related metabolic complications associate with impaired cognitive function and reduced hypothalamic neurosteroid concentration in mice

(A) Schematic illustration of the experimental strategy. Eight-week-old C57Bl/6J mice were fed with either chow or western diet for 16 consecutive weeks (16w-WD).

(B) Body weight profile (n = 10/genotype).

(C) Basal blood glucose concentration and (D) glucose tolerance test (n = 7/genotype).

(E) Insulin sensitivity test (n=10/genotype).

(F) Task learning curve for the latency to reach the scape hole during the training phase of the Barnes maze test (BMT) in mice fed with either chow or 16w-WD. Results show the average of 2 trials per day during 5 consecutive days (n = 7–8/diet).

(G–J) Parameters recorded to assess Barnes maze performance in mice, fed with either chow or 16w-WD, during the test phase: (G) latency to target hole, (H) time spent in target quadrant, (I) total distance traveled, and (J) representative traces of mouse movement trajectories (n = 7–8/genotype).

(K–N) Parameters recorded to assess NORT performance in mice, fed with either chow or 16w-WD, during the test phase: (K) discrimination index (time exploring novel object − time exploring familiar object)/(time exploring novel object + time exploring familiar object), (L) exploration time (time exploring novel object + time exploring familiar object), (M) total distance traveled, and (N) representative traces of mouse movement trajectories (n = 8–10/genotype).

(O–R) Recorded parameters to assess open-field performance in mice fed with either chow or 16w-WD: (O) time spent in the center, (P) number of entries in the center, (Q) total distance traveled, and (R) global activity (n = 10/genotype).

(S–U) Quantification of pregnenolone concentration in the (S) perirhinal cortex, (T) hippocampus, and (U) arcuate-enriched mediobasal hypothalamus in mice fed with either chow or 16w-WD (n = 9/genotype).

All studies were performed on male mice at 24–26 weeks of age. Dots in panels represent individual samples. Data are presented as mean ± SEM. ∗p < 0.01; ∗∗p < 0.01; ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001; ns, not significant.