Modulation of melanocortin signaling ameliorates uremic cachexia

Kidney International
W CheungRobert H Mak

Abstract

Insulin-like growth factor (IGF)-I increases muscle mass while myostatin inhibits its development. Muscle wasting is common in patients with uremic cachexia and may be due to imbalance of this regulation. We had proposed a central mechanism involving leptin and melanocortin signaling in the pathogenesis of uremic cachexia since agouti-related peptide (AgRP), a melanocortin-4 receptor antagonist, reduced uremic cachexia. Here we found that injection of AgRP into the cerebral ventricles resulted in a gain of body mass and improved metabolic rate regulation in a mouse model of uremic cachexia. These salutary effects occurred independent of increased protein and calorie intake. Myostatin mRNA and protein concentrations were increased while those of IGF-I were decreased in the skeletal muscle of uremic mice. AgRP treatment partially corrected these uremia-induced changes. Suppressor of cytokine signaling-2 gene expression (SOCS2) was significantly increased in uremic animals and AgRP reduced this expression. We suggest that AgRP improves uremic cachexia and muscle wasting by a peripheral mechanism involving the balance between myostatin and IGF-I.

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Citations

May 10, 2011·Cellular and Molecular Life Sciences : CMLS·Bart C De JongheKendra K Bence
Jan 30, 2010·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Wai W CheungRobert H Mak
Feb 8, 2011·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Robert H MakBethany J Foster
Aug 14, 2012·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Colin Farquharson, S Faisal Ahmed
Jul 18, 2008·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Jonas Axelsson
Aug 28, 2009·Seminars in Dialysis·Tae YamamotoJonas Axelsson
Aug 24, 2012·American Journal of Physiology. Renal Physiology·Wai W Cheung, Robert H Mak
Jan 9, 2010·Journal of the American Society of Nephrology : JASN·Liping ZhangWilliam E Mitch
Feb 26, 2011·Clinical Journal of the American Society of Nephrology : CJASN·Tetsu MiyamotoPeter Stenvinkel
Jul 2, 2014·Nature Reviews. Nephrology·Xiaonan H Wang, William E Mitch
Apr 30, 2013·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Ibrahim H Fahal
Feb 18, 2010·Expert Opinion on Drug Discovery·Mark Daniel Deboer
Aug 1, 2012·Kidney International·Robert H Mak, Wai W Cheung
Jul 2, 2008·Kidney International·Tiffany K Roberts, James L Bailey
Jan 5, 2011·Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation·Juan J Carrero
Apr 9, 2011·Journal of Cachexia, Sarcopenia and Muscle·Theodore P Braun, Daniel L Marks
Apr 9, 2011·Journal of Cachexia, Sarcopenia and Muscle·Robert H MakKamyar Kalantar-Zadeh
Jun 27, 2015·The Journal of Endocrinology·Maria Carolina S MendesJosé B C Carvalheira
Jun 19, 2013·The International Journal of Biochemistry & Cell Biology·Bradley S GordonScot R Kimball
Aug 6, 2013·The International Journal of Biochemistry & Cell Biology·Marie AmitaniAkio Inui
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Jul 11, 2014·Biochimie·Pascaline M AlixChristophe O Soulage
Aug 10, 2010·Current Opinion in Supportive and Palliative Care·Alessio MolfinoFilippo Rossi Fanelli
Oct 12, 2013·Journal of the American Society of Nephrology : JASN·Wai W CheungRobert H Mak
Aug 21, 2008·American Journal of Physiology. Endocrinology and Metabolism·Alessandro LavianoMarilia Seelaender
May 29, 2009·Current Opinion in Clinical Nutrition and Metabolic Care·Maurizio MuscaritoliFilippo Rossi Fanelli
Dec 19, 2019·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Yunan ZhouNaomi Clyne
Jan 1, 2012·Expert Review of Endocrinology & Metabolism·Eirini KyranaAnil Dhawan

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