Journal: Advanced Science
Article Title: Caspase‐6 Controls Lipid and Energy Metabolism in Diet‐Induced Obesity
doi: 10.1002/advs.202514784
Figure Lengend Snippet: Caspase‐6 cleaves PPARγ and SP1 to control ATGL expression in adipocytes. (A, B) Immunoblot of PPARγ and ATGL proteins in eWAT (A) and iWAT (B) of WT and C6KO mice fed 60% HFD for 12 weeks (n = 4). Two tailed unpaired Student's t ‐test. (C) In vitro cleavage of recombinant PPARγ by active caspase‐6. Immunoblot of PPARγ. (D) Immunoblot of lysates from 3T3‐L1 adipocytes treated with cycloheximide (5 µg/ml) and TNFα (25 ng/ml) for indicated time with or without pretreatment of Emricasan (50 µg/ml) for 1 hr. (E, F) Immunoblot SP1 protein in eWAT (E) and iWAT (F) of WT and C6KO mice fed HFD for 12 weeks (n = 3). Two tailed unpaired Student's t ‐test. (G) In vitro cleavage of recombinant SP1 by active caspase‐6. Coomassie blue staining of gel. (H) Immunoblot of lysates from 3T3‐L1 adipocytes treated with cycloheximide (CHX, 5 µg/ml) and TNFα (25 ng/ml) for indicated time with or without pretreatment of Emricasan (50 µg/ml) for 1 hr. (I) Immunoblot of lysates from ex vivo cultured eWAT from WT or C6KO, treated with CHX (15 µg/ml) and TNFα (75 ng/ml) for indicated time. (J) Pnpla2 expression in 3T3‐L1 adipocytes treated with Rosiglitazone (5µM) or T0070907 (100 nM) in the presence or absence of Mithramycin (10 µM) for 6 h (n = 3). Two tailed unpaired Student's t ‐test. (K) In vitro cleavage of WT and mutant (D69E) PPARγ2 expressed in HEK293T by recombinant active caspase‐6. (L) In vitro cleavage of WT and mutant (D185E) SP1 expressed in HEK293T by recombinant active caspase‐6. (M) PPARγ activity reporter assay in HEK293T cell expressing PPRE‐H2B‐eGFP along with WT PPARγ or PPARγ D69E mutant in the absence or presence of CHX‐TNFα treatment (n = 8). Two tailed unpaired Student's t ‐test. (N‐V) Pearson correlation between CASP6 and PPARγ target genes in human adipose tissues ( GSE245948 ): Correlation matrix (N), AQP7 (O), CPT1B (P), FADS2 (Q), ME3 (R), PLIN4 (S), PCK2 (T), SLC27A1 (U), and SLC27A4 (V). (n = 76). * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.
Article Snippet: Recombinant active caspase‐6 was obtained from Enzo Life Sciences (#BML‐SE170), recombinant PPARγ from Sino Biological (#12019‐H20B), and recombinant SP1 from Active Motif (#81181).
Techniques: Control, Expressing, Western Blot, Two Tailed Test, In Vitro, Recombinant, Staining, Ex Vivo, Cell Culture, Mutagenesis, Activity Assay, Reporter Assay