Intranasal application of the melanocortin 4 receptor agonist MSH/ACTH(4-10) in humans causes lipolysis in white adipose tissue

International Journal of Obesity

Volumn 36, Issue 5, 2012, Pages 703-708

  Wellhoner P ^a   Horster R ^a   Jacobs, F ^a   Sayk, F ^a   Lehnert, H ^a   Dodt, C ^b  

^a UNIVERSITY HOSPITAL SCHLESWIG HOLSTEIN   (Germany)

^b KLINIKUM BOGENHAUSEN   (Germany)

Author keywords

Adipose tissue; Melanocortins; Microdialysis; Microneurography; Sympathetic nerve system

Indexed keywords

CORTICOTROPIN[4-10]; GLYCEROL; MELANOCORTIN 4 RECEPTOR; NITROPRUSSIDE SODIUM; PLACEBO;

ABDOMEN; ADRENERGIC SYSTEM; ADULT; ARTICLE; BLOOD FLOW; BLOOD PRESSURE; BODY WEIGHT; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG INFUSION; ENERGY METABOLISM; HEART RATE; HUMAN; LIPOLYSIS; MALE; MICRODIALYSIS; NORMAL HUMAN; PERONEUS NERVE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SKELETAL MUSCLE; SYMPATHETIC NERVE; VOLUNTEER; WHITE ADIPOSE TISSUE;

ABDOMINAL FAT; ADIPOSE TISSUE, WHITE; ADMINISTRATION, INTRANASAL; ADRENOCORTICOTROPIC HORMONE; ADULT; BLOOD PRESSURE; BODY WEIGHT; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; ENERGY METABOLISM; GLYCEROL; HEART RATE; HUMANS; LIPOLYSIS; MALE; MICRODIALYSIS; MUSCLE, SKELETAL; NOOTROPIC AGENTS; PEPTIDE FRAGMENTS; RECEPTOR, MELANOCORTIN, TYPE 4; SYMPATHETIC NERVOUS SYSTEM;

ANIMALIA;

EID: 84860729198     PISSN: 03070565     EISSN: 14765497     Source Type: Journal    
DOI: 10.1038/ijo.2011.105     Document Type: Article

References (28)

1. Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 1998; 19: 155-157.
2. Fehm HL, Smolnik R, KernW, McGregor GP, Bickel U, Born J. The melanocortin melanocyte-stimulating hormone/adrenocorticotropin( 4-10) decreases body fat in humans. J Clin Endocrinol Metab 2001; 86: 1144-1148.
3. Tian X, Switzer AG, Derose SA, Mishra RK, Solinsky MG, Mumin RN et al. Discovery of orally bioavailable 1,3,4-trisubstituted 2-oxopiperazine-based melanocortin-4 receptor agonists as potential antiobesity agents. J Med Chem 2008; 51: 6055-6066.
4. Nogueiras R, Wiedmer P, Perez-Tilve D, Veyrat-Durebex C, Keogh JM, Sutton GM et al. The central melanocortin system directly controls peripheral lipid metabolism. J Clin Invest 2007; 117: 3475-3488.
5. Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL. Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci 2002; 5: 514-516.
6. Dodt C, Keyser B, Molle M, Fehm HL, Elam M. Acute suppression of muscle sympathetic nerve activity by hydrocortisone in humans. Hypertension 2000; 35: 758-763.
7. Enoksson S, Nordenstrom J, Bolinder J, Arner P. Influence of local blood flow on glycerol levels in human adipose tissue. Int J Obes Relat Metab Disord 1995; 19: 350-354.
8. Hoch M, Eberle AN, Wagner U, Bussmann C, Peters T, Peterli R. Expression and localization of melanocortin-1 receptor in human adipose tissues of severely obese patients. Obesity(Silver Spring) 2007; 15: 40-49.
9. Hoch M, Hirzel E, Lindinger P, Eberle AN, Linscheid P, Martin I et al. Weak functional coupling of the melanocortin-1 receptor expressed in human adipocytes. J Recept Signal Transduct Res 2008; 28: 485-504.
10. Bowers RR, Festuccia WT, Song CK, Shi H, Migliorini RH, Bartness TJ. Sympathetic innervation of white adipose tissue and its regulation of fat cell number. Am J Physiol Regul Integr Comp Physiol 2004; 286: R1167-R1175.
11. Brito MN, Brito NA, Baro DJ, Song CK, Bartness TJ. Differential activation of the sympathetic innervation of adipose tissues by melanocortin receptor stimulation. Endocrinology 2007; 148: 5339-5347.
12. Song CK, Jackson RM, Harris RB, Richard D, Bartness TJ. Melanocortin-4 receptor mRNA is expressed in sympathetic nervous system outflow neurons to white adipose tissue. Am J Physiol Regul Integr Comp Physiol 2005; 289: R1467-R1476.
13. Dodt C, Lonnroth P, Fehm HL, Elam M. Intraneural stimulation elicits an increase in subcutaneous interstitial glycerol levels in humans. J Physiol (Lond) 1999; 521 (Part 2): 545-552.
14. Jacob S, Hauer B, Becker R, Artzner S, Grauer P, Loblein K et al. Lipolysis in skeletal muscle is rapidly regulated by low physiological doses of insulin. Diabetologia 1999; 42: 1171-1174.
15. Kurpad AV, Khan K, Calder AG, Elia M. Muscle and whole body metabolism after norepinephrine. Am J Physiol 1994; 266 (Part 1): E877-E884.
16. Maggs DG, Jacob R, Rife F, Lange R, Leone P, During MJ et al. Interstitial fluid concentrations of glycerol, glucose, and amino acids in human quadricep muscle and adipose tissue. Evidence for significant lipolysis in skeletal muscle. J Clin Invest 1995; 96: 370-377.
17. Rohner-Jeanrenaud F. Neuroendocrine regulation of nutrient partitioning. Ann NY Acad Sci 1999; 892: 261-271.
18. Hagstrom-Toft E, Qvisth V, Nennesmo I, Ryden M, Bolinder H, Enoksson S et al. Marked heterogeneity of human skeletal muscle lipolysis at rest. Diabetes 2002; 51: 3376-3383.
19. Hallschmid M, Smolnik R, McGregor G, Born J, Fehm HL. Overweight humans are resistant to the weight-reducing effects of melanocortin4-10. J Clin Endocrinol Metab 2006; 91: 522-525.
20. Krishna R, Gumbiner B, Stevens C, Musser B, Mallick M, Suryawanshi S et al. Potent and selective agonism of the melanocortin receptor 4 with MK-0493 does not induce weight loss in obese human subjects: energy intake predicts lack of weight loss efficacy. Clin Pharmacol Ther 2009; 86: 659-666.
21. Shinyama H, Masuzaki H, Fang H, Flier JS. Regulation of melanocortin-4 receptor signaling: agonist-mediated desensitization and internalization. Endocrinology 2003; 144: 1301-1314.
22. Clark AJ, Baig AH, Noon L, Swords FM, Hunyady L, King PJ. Expression, desensitization, and internalization of the ACTH receptor (MC2R). Ann NY Acad Sci 2003; 994: 111-117.
23. Mohammad S, Baldini G, Granell S, Narducci P, Martelli AM, Baldini G. Constitutive traffic of melanocortin-4 receptor in Neuro2A cells and immortalized hypothalamic neurons. J Biol Chem 2007; 282: 4963-4974.
24. Sayk F, Heutling D, Dodt C, Iwen KA, Wellhoner JP, Scherag S et al. Sympathetic function in human carriers of melanocortin-4 receptor gene mutations. J Clin Endocrinol Metab 2010; 95: 1998-2002.
25. Garruti G, Giusti V, Nussberger J, Darimont C, Verdumo C, Amstutz C et al. Expression and secretion of the atrial natriuretic peptide in human adipose tissue and preadipocytes. Obesity (Silver Spring) 2007; 15: 2181-2189.
26. Birkenfeld AL, Boschmann M, Moro C, Adams F, Heusser K, Franke G et al. Lipid mobilization with physiological atrial natriuretic peptide concentrations in humans. J Clin Endocrinol Metab 2005; 90: 3622-3628.
27. Moro C, Crampes F, Sengenes C, de Glisezinski I, Galitzky J et al. Atrial natriuretic peptide contributes to physiological control of lipid mobilization in humans. FASEB J 2004; 18: 908-910.
28. Birkenfeld AL, Budziarek P, Boschmann M, Moro C, Adams F, Franke G et al. Atrial natriuretic peptide induces postprandial lipid oxidation in humans. Diabetes 2008; 57: 3199-3204.