Fig. 3: Targeting transcriptional regulators of lysosomal function in adipocytes attenuates lipolysis with prolonged fasting.
From: Non-canonical lysosomal lipolysis drives mobilization of adipose tissue energy stores with fasting
a Schematic of tamoxifen-inducible adipocyte-specific Tfeb loss of function (KO) relative to controls (FLOX), using mice that were 8 weeks old at study start. Paired blood draws were used to assess the lipolytic response to adrenergic stimulus (isoproterenol) and fasting. For panels d and f–j, data show mean, S.D.M. b. Change in plasma non-esterified fatty acids (NEFA) with isoproterenol (ISO) or fast: FLOX n = 9 (6 male, 3 female); KO n = 13 (7 male, 6 female). Two-way ANOVA to assess genotype effect. c Change in plasma glycerol with isoproterenol (ISO) or fast. FLOX n = 9 (6 male, 3 female); KO n = 13 (7 male, 6 female). ****p < 0.0001, two-way ANOVA to assess genotype effect. d qPCR analyses of isolated adipocytes in control mice (FLOX) or adipocyte specific Tfeb loss of function (KO) (n = 9 FLOX; n = 13 KO). Two-way ANOVA to assess genotype effect. e Immunoblots of gonadal adipose tissues (gWAT) for LAL, TFEB, and ATGL collected at the 24-hour fasting timepoint. Note: tubulin control was run on a different gel. f qPCR analyses of glucose metabolism genes in isolated adipocytes from control mice (FLOX) or adipocyte specific Tfeb loss of function (KO) mice (n = 9 FLOX; n = 13 KO). Two-way ANOVA to assess genotype effect, *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. g Terminal plasma glucose in control mice (FLOX) or adipocyte specific Tfeb loss of function (KO). FLOX n = 9 (6 male, 3 female); KO n = 13 (7 male, 6 female). Significance assessed by two-tailed t-test. h Terminal plasma ketones in control mice (FLOX) or adipocyte specific Tfeb loss of function (KO). FLOX n = 9 (6 male, 3 female); KO n = 13 (7 male, 6 female). Significance assessed by two-tailed t-test. i Change in body weight. FLOX n = 9 (6 male, 3 female); KO n = 13 (7 male, 6 female). Significance assessed by two-tailed t-test. j Terminal plasma fibroblast growth factor 21 (FGF21) levels measured by ELISA: FLOX n = 9 (6 male, 3 female). Significance assessed by two-tailed t-test.
