FIGURE SUMMARY
Title

Inhibition of mitochondrial citrate shuttle alleviates metabolic syndromes induced by high-fat diet

Authors
Wang, J.X., Zhang, Y.Y., Qian, Y.C., Qian, Y.F., Jin, A.H., Wang, M., Luo, Y., Qiao, F., Zhang, M.L., Chen, L.Q., Du, Z.Y.
Source
Full text @ Am. J. Physiol. Cell Physiol.
Fig. 1

Structure and expression distribution of fish Slc25a1 is similar to that of mammals. A: protein three-dimensional (3-D) structure of SLC25A1s. B: evolutionary tree of SLC25A1s. C: multiple sequence comparison of SLC25A1S. D and E: zebrafish slc25a1a and slc25a1b mRNA expression in several tissues (n = 4–6).

Fig. 2

Blocking mitochondrial citrate export attenuates high-fat diet (HFD)-induced obesity. A: weight gain ratio (n = 3). B: condition factor (n = 24). C: viscerosomatic index (n = 24). D: carcass ratio (n = 24). E: plasma alanine aminotransferase (ALT) activity (n = 4–6). F: plasma β-HB content (n = 6). G: hepatic hematoxylin and eosin (H&E) section. H and I: protein expression of hepatic Slc25a1 and ACLY in zebrafish and Nile tilapia (n = 2–3). Values are means ± SD. The asterisk symbol indicates significant differences from the control treatment at *P < 0.05, **P < 0.01, ***P < 0.001 (independent-sample t test).

Fig. 3

Slc25a1 inhibition attenuates high-fat diet (HFD)-induced hyperglycemia by increasing glucose uptake but not use. A: plasma glucose levels (n = 5–6). B: plasma insulin levels (n = 6). C: glucose tolerance test of zebrafish (n = 5–6). D: mRNA expression of hepatic chrebp, glut2, and insrb in zebrafish (n = 5–7). E: hepatic glycogen in zebrafish (n = 6). F: hepatic glycolysis-related metabolites in zebrafish, n = 4. G: mRNA expression of hepatic pfk and pk in zebrafish (n = 5–7). H: mRNA expression of hepatic ldha, ldhba, and ldhbb in zebrafish (n = 5–7). I: mRNA expression of hepatic pca and pcb in zebrafish (n = 5–7). J and K: protein expression of hepatic Pdk4 and p-Pdhe1α in zebrafish and Nile tilapia (n = 2–3). L: rate of d-[1-14C]-glucose oxidation in primary hepatocytes of Nile tilapia (n = 3). M: glucose metabolism patterns after inhibition of Slc25a1 under HFD. Values are means ± SD. The asterisk symbol indicates significant differences from the control treatment at *P < 0.05, **P < 0.01, ***P < 0.001 (independent-sample t test). Figure created with BioRender.com.

Fig. 4

Slc25a1 inhibition attenuates high-fat diet (HFD)-induced abnormal hepatic lipid deposition by enhancing oxidative catabolism. A: hepatic triglyceride(TAG) content in zebrafish (n = 6). B: hepatic nonesterified fatty acid (NEFA) content in zebrafish (n = 6). C–F: mRNA expression of hepatic liposynthesis- and lipid catabolism-related genes in zebrafish (n = 5–7). G and I: protein expression of hepatic carnitine palmitoyltransferase 1a (Cpt1a) in zebrafish and Nile tilapia (n = 2–3). H: hepatic TAG content in Nile tilapia (n = 6). J and K: rate of [1-14C]- palmitic acid (PA) oxidation in vitro and in vivo (n = 3 and 6, respectively). L: lipid metabolism patterns after inhibition of Slc25a1 under HFD. Values are means ± SD. The asterisk symbol indicates significant differences from the control treatment at *P < 0.05, **P < 0.01, ***P < 0.001 (independent-sample t test). Figure created with BioRender.com.

Fig. 5

Slc25a1 inhibition enhances mitochondrial oxidative phosphorylation and proliferation in a high-fat diet (HFD). A and B: hepatic TCA cycle and oxidative phosphorylation-related gene expression and metabolites in zebrafish (n = 4 and 5–7, respectively). C: hepatic mtDNA in zebrafish (n = 6). D: mRNA expression of hepatic pgc1αa and pgc1αb in zebrafish (n = 5–7). E: mitochondrial metabolic patterns after inhibition of Slc25a1 under HFD. Values are means ± SD. The asterisk symbol indicates significant differences from the control treatment at *P < 0.05, **P < 0.01, ***P < 0.001 (independent-sample t test). Figure created with BioRender.com.

Fig. 6

Inhibition of Slc25a1 remodels protein acetylation modification in zebrafish liver under high-fat diet (HFD). A: hepatic acetyl-CoA content in zebrafish (n = 6). B: mRNA expression of hepatic sirts in zebrafish (n = 5–7). C: protein expression of hepatic Acss2 in zebrafish (n = 3). D and E: levels of pan-acetylation in zebrafish liver cell line (ZFL) and zebrafish liver. F: protein expression of hepatic ac-Cpa1a and ac-Pdhe1α in zebrafish (n = 2). G: hepatic acetyl-CoA content in Nile tilapia (n = 6). H: protein expression of hepatic ac-Cpa1a and ac-Pdhe1α in Nile tilapia (n = 2). I: the shift in acetylation paradigms after inhibition of Slc25a1 under HFD. Values are means ± SD. The asterisk symbol indicates significant differences from the control treatment at *P < 0.05, **P < 0.01, ***P < 0.001 (independent-sample t test). Figure created with BioRender.com.

Acknowledgments
This image is the copyrighted work of the attributed author or publisher, and ZFIN has permission only to display this image to its users. Additional permissions should be obtained from the applicable author or publisher of the image. Full text @ Am. J. Physiol. Cell Physiol.
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