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. 2022 Mar 24;11:e67368. doi: 10.7554/eLife.67368

Figure 4. The antiobesity effect of sulforaphane (SFN) is NRF2-dependent and HDAC6-independent.

(A–H) NRF2 KO mice were placed on high-fat diet (HFD) to induce obesity. Mice were then treated daily by i.p. vehicle or SFN injections. SFN dose was 5 mg/kg for the first three weeks and increased to 10 mg/kg thereafter. Wild-type diet-induced obese (DIO) mice were treated with vehicle or SFN for the same period for comparison. (A, B) Body weight (A) and percent change in body weight (B) of the NRF2 KO mice throughout the vehicle or SFN treatments. (C) Body weight of NRF2 KO (the same cohort graphed in A) and wild-type DIO mice receiving treatments with vehicle or SFN for the same period for comparison. (D) Percent change in body weight of NRF2 KO and wild-type DIO mice at the end of the treatments shown in panel (C). (E, F) Daily food intake (E) and cumulative food intake (F) of the DIO NRF2 KO mice (n = 6 per group) during the treatment period. (G, H) Glucose tolerance test (GTT) (G) and the area under the curve (AUC) of the GTT (H) performed on NRF2 KO DIO mice (n = 6, 8) during the 3 weeks of vehicle or 5 mg/kg SFN treatment shown in (A). (I–K) HDAC6 KO or wild-type mice were fed HFD to induce obesity. The mice were then treated with vehicle or 5 mg/kg SFN by daily i.p. injections. Body weights (I), percent change in body weight (J), and daily food intakes (K) were recorded (n = 4–6 mice per group). *p<0.05, **p<0.01, ***p<0.001 by two-way ANOVA with Sidak correction (A–I).

Figure 4.

Figure 4—figure supplement 1. Effect of sulforaphane (SFN) on tubulin acetylation in mouse embryonic fibroblasts (MEFs).

Figure 4—figure supplement 1.

MEFs treated with DMSO as vehicle, SFN or the HDAC6-specific inhibitor Tubastatin A HCl (TubA) at the indicated doses for 24 hr. Tubulin acetylation (K40) was analyzed by Western blotting.
Figure 4—figure supplement 2. Sulforaphane (SFN) does not induce a beige or brown adipose-specific gene expression profile.

Figure 4—figure supplement 2.

(A, B) Diet-induced obese (DIO) wild-type mice were treated with vehicle or 5 mg/kg SFN for 1 week (n = 6–7 per group). The expression of brown adipose, beige adipose, and mitochondrial genes in inguinal white adipose tissue (iWAT) (A) and brown adipose tissue (BAT) (B) were analyzed by qPCR. (C–F) The fragments per kilobase of transcript per million mapped reads (FKPM) values of the BAT marker genes in iWAT of vehicle or SFN-treated DIO NRF2 KO mice. p-adjusted values (false discovery rate [FDR]) are indicated over the bar graphs. *padj<0.05, **padj<0.01 (See also Supplementary file 2). (G–I) The expression of beige-specific (G) and brown-related genes (H) and of Nqo1 (I) in iWAT explants (n = 4–6 per group) from DIO wild-type mice were treated with vehicle or indicated doses of SFN for 24 hr. Gene expression was analyzed by qPCR. *p<0.05, **p<0.01, ***p<0.001 by Student’s t-test.