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. 2017 Nov 30;8:1878. doi: 10.1038/s41467-017-01878-6

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Hepatic Crtc2 controls systemic glucose and lipid metabolism in mammals. a Glucose tolerance test (GTT, left), pyruvate tolerance test (PTT, middle), and insulin tolerance test (ITT, right) showing effects of chronic depletion of hepatic Crtc2 in mice under HFD for 8 weeks on glucose metabolism and insulin signaling (n = 13 for Crtc2 ^f/f mice and n = 11 for Crtc2 ^LKO mice). Area under the curve (AUC) for each test was also shown. b Ad libitum (fed) or 16 h-fasting (fasted) blood glucose levels (left), and ad libitum (fed) or 16 h-fasting (fasted) insulin levels (right) from either Crtc2 ^f/f mice or Crtc2 ^LKO mice under HFD for 9 weeks (n = 13 for Crtc2 ^f/f mice and n = 11 for Crtc2 ^LKO mice). c Plasma triglycerides (TG) levels (left) and hepatic TG levels (right) from either Crtc2 ^f/f mice or Crtc2 ^LKO mice under ad libitum (fed) or 16 h-fasting (fasted) conditions under HFD for 9 weeks (n = 13 for Crtc2 ^f/f mice and n = 11 for Crtc2 ^LKO mice). d Paraffin-embedded sections of liver tissues from 8-week HFD-fed mice were stained with hematoxylin and eosin (H&E, left). Frozen liver sections were also stained with oil red O (right). Data represent three independent experiments (n = 3 mice per group). e Paraffin-embedded sections of subcutaneous white adipose tissues (scWAT, left), visceral white adipose tissues (visWAT, middle), and brown adipose tissues (BAT, right) from 16 h-fasted, 9-week HFD-fed Crtc2 ^f/f mice or Crtc2 ^LKO mice were stained with H&E. Data represent three independent experiments (n = 3 mice per group). f Body weight from either Crtc2 ^f/f mice or Crtc2 ^LKO mice under HFD (n = 13 for Crtc2 ^f/f mice and n = 11 for Crtc2 ^LKO mice). g Energy expenditure (top and bottom left for quantitation) and locomotor activity (bottom right) were measured from 7-week HFD-fed Crtc2 ^f/f mice or Crtc2 ^LKO mice by using metabolic cage (n = 10 for Crtc2 ^f/f mice and n = 9 for Crtc2 ^LKO mice). Note that the HFD was initiated at 4 weeks of age and maintained throughout the experimental period. Data in a, b, c, f and g represent mean ± s.e.m. (*P < 0.05, **P < 0.01, t-test a–c and g or Tukey–Kramer multiple comparisons f)