Volume 11, Issue 1, Pages (January 2010)

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Presentation transcript:

Volume 11, Issue 1, Pages 77-83 (January 2010) Endogenous Leptin Signaling in the Caudal Nucleus Tractus Solitarius and Area Postrema Is Required for Energy Balance Regulation Matthew R. Hayes, Karolina P. Skibicka, Theresa M. Leichner, Douglas J. Guarnieri, Ralph J. DiLeone, Kendra K. Bence, Harvey J. Grill Cell Metabolism Volume 11, Issue 1, Pages 77-83 (January 2010) DOI: 10.1016/j.cmet.2009.10.009 Copyright © 2010 Elsevier Inc. Terms and Conditions

Figure 1 Leptin Receptor Knockdown in the mNTS and AP Increases Daily Caloric Intake (A and B) Representative immunofluorescent analysis showing the extent of AAV-shCtrl (A) and AAV-LepR (B) spread, with EGFP-expressing neurons being identified in nuclei that contain the LepR: mNTS and AP. EGFP-expressing neurons are also found in non-LepR-expressing nuclei: DMV, dorsolateral NTS (SolDL), and solitary commissural (SolC). cc, central canal. (C) Representative qPCR reveals significant suppression in LepR mRNA in mNTS/AP micropunched tissue for AAV-LepR-treated rats compared to AAV-shCtrl rats. ∗p < 0.05. (D) Daily Kcal intake for LepRKD and shCtrl rats pre- and postviral delivery while maintained on chow or high fat (HF) diet (60% Kcal from fat). ∗ = p < 0.05 for bracketed weekly averages. Cell Metabolism 2010 11, 77-83DOI: (10.1016/j.cmet.2009.10.009) Copyright © 2010 Elsevier Inc. Terms and Conditions

Figure 2 Increased Body Weight Gain Following Knockdown of mNTS/AP LepR Cumulative body weight of chow-maintained LepRKD and shCtrl rats pre- and post-mNTS/AP-directed AAV delivery. ∗p < 0.05 for bracketed weekly averages. (Inset) Graph shows inguinal and total WAT mass for LepRKD and shCtrl rats. ∗p < 0.05. Cell Metabolism 2010 11, 77-83DOI: (10.1016/j.cmet.2009.10.009) Copyright © 2010 Elsevier Inc. Terms and Conditions

Figure 3 Endogenous LepR Signaling in mNTS/AP Neurons Is Required for the Intake-Suppressive Effects of CCK and Controls for Food Intake via an AMPK-Dependent Mechanism (A) Cumulative 15% sucrose intake following i.p. injection of CCK (3 μg/kg) or vehicle (0.9% saline) for LepRKD and shCtrl rats pre- and 4 weeks post-mNTS-directed AAV delivery. ∗p < 0.05. (B) LepRKD rats showed increased pAMPKα2 levels in mNTS/AP micropunched tissue compared to shCtrl rats under ad libitum-fed conditions. Representative immunoblots for total AMPK and pAMPKα2 are shown. Relative pAMPKα2 = the ratio of pAMPKα2 to total AMPK. ∗p < 0.05. (C) Cumulative chow intake for LepRKD and shCtrl rats following fourth i.c.v. delivery of compound C (15μg) or vehicle (DMSO). ∗p < 0.05. Cell Metabolism 2010 11, 77-83DOI: (10.1016/j.cmet.2009.10.009) Copyright © 2010 Elsevier Inc. Terms and Conditions