Original ResearchFull Report: Basic and Translational—LiverCentral Melanin-Concentrating Hormone Influences Liver and Adipose Metabolism Via Specific Hypothalamic Nuclei and Efferent Autonomic/JNK1 Pathways
Section snippets
Animals and Surgery
For all experiments, 8- to 10-week-old (250–300 g) male Sprague–Dawley rats were used (see the Supplementary Materials and Methods section).
Energy Expenditure, Locomotor Activity, Respiratory Quotient, and Lipid Use
These parameters were analyzed using a cage calorimetry system (LabMaster; TSE Systems, Thuringia, Germany)19 (see the Supplementary Materials and Methods section).
Quantitative Reverse-Transcription Polymerase Chain Reaction Procedure
RNA was extracted using TRIzol reagent (Invitrogen, Paisley, UK) according to the manufacturer's instructions and as previously described.19 Primer sequences are described in Supplementary Table 1
The CNS-MCH System Controls Adiposity Independent of Food Intake
Central infusion of MCH increased food intake in ad libitum–fed rats (MCH-ad lib) (Figure 1A). A second control group of intracerebroventricular (ICV) MCH–infused animals was pair-fed to match the intake of saline-infused controls (MCH-pf). Weight gain (Figure 1B), metabolic efficiency (Figure 1C), and fat mass gain (Figure 1D) of ICV MCH-ad lib and MCH-pf rats was significantly higher than that of controls. Non–fat mass was increased significantly after central infusion of MCH only in rats fed
Discussion
We report here that the central MCH system directly controls peripheral lipid metabolism. Specifically, we show that central infusion of MCH stimulates lipid absorption and lipid deposition in WAT and liver independently of its orexigenic action or changes in energy expenditure. Our results suggest a molecular basis for a CNS MCH-induced switch in nutrient partitioning and substrate use. Those actions likely occur through effects on 2 different pathways: the SNS mediates the effects of CNS MCH
Acknowledgments
The authors deeply thank Professor Antonio Vidal-Puig and Dr Sergio Rodríguez-Cuenca (University of Cambridge, UK) for kindly revising and critically reading the article.
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by grants from the Ministerio de Educacion y Ciencia (BFU2011 to C.D., RyC-2007-00211 to M.L., RYC-2008-02219 and SAF2009-07049 to R.N.; RYC-2009-04972 and SAF2010-19347 to G.S.), Xunta de Galicia (10PXIB208164PR to M.L., and 2010/14 to R.N.), Fondo Investigationes Sanitarias (PS09/01880 to M.L.); Swiss National Science Foundation, Bern, Switzerland number 31003A-134919/1 (F.R.J.). CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIII and is supported by the US National Institutes of Health (grant HL084207) and the American Diabetes Association (grant 1-11-BS-127 to K.R.). The research leading to these results also has received funding from the European Community's Seventh Framework Programme under grant agreements (number 245009: “NeuroFAST” to C.D., M.L., and R.N., ERC-2010-StG-OBECAN-260464 to G.S.; and ERC-2011-StG-OBESITY53-281408 to R.N.).
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Authors share co-first authorship.