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[Preprint]. 2023 Apr 13:2023.04.12.536558. [Version 1] doi: 10.1101/2023.04.12.536558

Extended Data Figure 3. FGF-21-induced increases in renal lipolysis promote increased renal gluconeogenesis in metabolic stress.

Extended Data Figure 3.

(A) Whole-body lipolysis (palmitate turnover) in mice infused with FGF-21±pretreatment with propranolol. In panels (A), (Q)-(V), groups were compared by ANOVA with Tukey’s multiple comparisons test. In panels (A)-(C), n=5 per group. (B)-(C) Kidney acetyl- and long-chain acyl-CoA concentrations in fed/fasted mice. (D)-(E) Kidney acetyl- and long-chain acyl-CoA concentrations in mice in DKA (n=6 per group). (F)-(G) Kidney acetyl- and long-chain acyl-CoA concentrations in a mouse model of NASH (n=8 per group). (H) Plasma non-esterified fatty acid concentrations in 24 hr fasted FGF-21f/f;Alb-CreERT2 mice (i.e. liver-specific FGF-21 knockout) (n=3 per group). (I)-(J) Kidney acetyl- and long-chain acyl-CoA concentrations. (K) Plasma NEFA in Klbf/f;Camk2a-Cre mice (i.e. brain-specific Klb knockout). In panels (K)-(M), n=5 per group. (L)-(M) Kidney acetyl- and long-chain acyl-CoA concentrations (n=5 per group). (N) Plasma NEFA in ICV FGF-21 infused rats. In panels (N)-(P), n=4 vehicle-treated and 5 FGF-21-treated rats per group. (O)-(P) Kidney acetyl- and long-chain acyl-CoA concentrations. (Q) Plasma NEFA in vehicle and FGF-21-infused mice, some pre-treated with chemical sympathectomy via 6-OHDA (in panels (Q)-(S), n=4 per group). (R)-(S) Kidney acetyl- and long-chain acyl-CoA concentrations. (T) Plasma NEFA in FGF-21-infused mice, some treated with antagonists of Adrb1 or Adrb2 (in panels (T)-(V), n=6 vehicle- or Adrb2 antagonist-treated mice, or 5 Adrb1 antagonist-treated mice). (U)-(V) Kidney acetyl- and long-chain acyl-CoA concentrations. (W) Plasma NEFA in WT and whole-body Adrb2 KO mice (n=4 vehicle-treated or 5 FGF-21-treated mice per group). (X) Whole-body palmitate turnover in Atglf/f;Ksp-Cre mice infused with FGF-21 or vehicle, and their WT littermates (n=6 per group, with the exception of WT+FGF-21-treated mice, in which n=7 per group). Unless otherwise specified, groups were compared by the 2-tailed unpaired Student’s t-test. In all panels, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.