Leptin treatment reduces body fat but does not affect lean body mass or the myostatin-follistatin-activin axis in lean hypoleptinemic women

American Journal of Physiology - Endocrinology and Metabolism

Volumn 301, Issue 1, 2011, Pages

  Brinkoetter, Mary ^a   Magkos, Faidon ^a   Vamvini, Maria ^a   Mantzoros, Christos S ^a,b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

Fat free mass; Muscle mass; Reproductive dysfunction

Indexed keywords

ACTIVIN; FOLLISTATIN; LEPTIN; METRELEPTIN; MYOSTATIN; PLACEBO; RECOMBINANT HORMONE; UNCLASSIFIED DRUG;

ADULT; AMENORRHEA; ARTICLE; BODY FAT; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG DOSE INCREASE; ENDOCRINE DISEASE; EVENING DOSAGE; EXERCISE; FEMALE; HORMONE BLOOD LEVEL; HUMAN; HYPOLEPTINEMIA; LEAN BODY WEIGHT; MENSTRUATION; MORNING DOSAGE; MUSCLE GROWTH; OPEN STUDY; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; TREATMENT DURATION;

ACTIVINS; ADIPOSE TISSUE; ADULT; BODY COMPOSITION; BODY WEIGHT; DOUBLE-BLIND METHOD; DOWN-REGULATION; FEMALE; FOLLISTATIN; HUMANS; LEPTIN; METABOLIC DISEASES; MYOSTATIN; PLACEBOS; SIGNAL TRANSDUCTION; THINNESS; YOUNG ADULT;

EID: 79959595133     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00146.2011     Document Type: Article

References (34)

1. Ballor DL, Keesey RE. A meta-analysis of the factors affecting exerciseinduced changes in body mass, fat mass and fat-free mass in males and females. Int J Obes 15: 717-726, 1991.
2. Ballor DL, Poehlman ET. Exercise-training enhances fat-free mass preservation during diet-induced weight loss: a meta-analytical finding. Int J Obes Relat Metab Disord 18: 35-40, 1994.
3. Chan JL, Matarese G, Shetty GK, Raciti P, Kelesidis I, Aufiero D, De Rosa V, Perna F, Fontana S, Mantzoros CS. Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans. Proc Natl Acad Sci USA 103: 8481-8486, 2006.
4. Chen YW, Gregory CM, Scarborough MT, Shi R, Walter GA, Vandenborne K. Transcriptional pathways associated with skeletal muscle disuse atrophy in humans. Physiol Genomics 31: 510-520, 2007.
5. Choi SJ, Yablonka-Reuveni Z, Kaiyala KJ, Ogimoto K, Schwartz MW, Wisse BE. Increased Energy Expenditure and Leptin Sensitivity Account for Low Fat Mass in Myostatin Deficient Mice. Am J Physiol Endocrinol Metab (First published March 22, 2011). doi:10.1152/ ajpendo.00656.2010.
6. Chou SH, Chamberland JP, Liu X, Matarese G, Gao C, Stefanakis R, Brinkoetter MT, Gong H, Arampatzi K, Mantzoros CS. Leptin is an effective treatment for hypothalamic amenorrhea. Proc Natl Acad Sci USA 108: 6585-6590, 2011.
7. Dardeno TA, Chou SH, Moon HS, Chamberland JP, Fiorenza CG, Mantzoros CS. Leptin in human physiology and therapeutics. Front Neuroendocrinol 31: 377-393, 2010.
8. Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, Sanna V, Jebb SA, Perna F, Fontana S, Lechler RI, DePaoli AM, O'Rahilly S. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 110: 1093-1103, 2002.
9. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 395: 763-770, 1998.
10. Gibson WT, Farooqi IS, Moreau M, DePaoli AM, Lawrence E, O'Rahilly S, Trussell RA. Congenital leptin deficiency due to homozygosity for the Delta133G mutation: report of another case and evaluationof response to four years of leptin therapy. J Clin Endocrinol Metab 89: 4821-4826, 2004.
11. Gonzalez-Cadavid NF, Taylor WE, Yarasheski K, Sinha-Hikim I, Ma K, Ezzat S, Shen R, Lalani R, Asa S, Mamita M, Nair G, Arver S, Bhasin S. Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting. Proc Natl Acad Sci USA 95: 14938-14943, 1998.
12. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269: 543-546, 1995.
13. Heymsfield SB, Greenberg AS, Fujioka K, Dixon RM, Kushner R, Hunt T, Lubina JA, Patane J, Self B, Hunt P, McCamish M. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 282: 1568-1575, 1999.
14. Hill JJ, Davies MV, Pearson AA, Wang JH, Hewick RM, Wolfman NM, Qiu Y. The myostatin propeptide and the follistatin-related gene are inhibitory binding proteins of myostatin in normal serum. J Biol Chem 277: 40735-40741, 2002.
15. Hukshorn CJ, Menheere PP, Westerterp-Plantenga MS, Saris WH. The effect of pegylated human recombinant leptin (PEG-OB) on neuroendocrine adaptations to semi-starvation in overweight men. Eur J Endocrinol 148: 649-655, 2003.
16. Lakshman KM, Bhasin S, Corcoran C, Collins-Racie LA, Tchistiakova L, Forlow SB, St Ledger K, Burczynski ME, Dorner AJ, Lavallie ER. Measurement of myostatin concentrations in human serum: Circulating concentrations in young and older men and effects of testosterone administration. Mol Cell Endocrinol 302: 26-32, 2009.
17. Lee JH, Chan JL, Sourlas E, Raptopoulos V, Mantzoros CS. Recombinant methionyl human leptin therapy in replacement doses improves insulin resistance and metabolic profile in patients with lipoatrophy and metabolic syndrome induced by the highly active antiretroviral therapy. J Clin Endocrinol Metab 91: 2605-2611, 2006.
18. Lee SJ. Regulation of muscle mass by myostatin. Annu Rev Cell Dev Biol 20: 61-86, 2004.
19. Lee SJ, Lee YS, Zimmers TA, Soleimani A, Matzuk MM, Tsuchida K, Cohn RD, Barton ER. Regulation of muscle mass by follistatin and activins. Mol Endocrinol 24: 1998-2008, 2010.
20. Ma K, Mallidis C, Bhasin S, Mahabadi V, Artaza J, Gonzalez- Cadavid N, Arias J, Salehian B. Glucocorticoid-induced skeletal muscle atrophy is associated with upregulation of myostatin gene expression. Am J Physiol Endocrinol Metab 285: E363-E371, 2003.
21. McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 387: 83-90, 1997.
22. McPherron AC, Lee SJ. Suppression of body fat accumulation in myostatin-deficient mice. J Clin Invest 109: 595-601, 2002.
23. Midorikawa T, Sekiguchi O, Beekley MD, Bemben MG, Abe T. A comparison of organ-tissue level body composition between college-age male athletes and nonathletes. Int J Sports Med 28: 100-105, 2007.
24. Moon HS, Matarese G, Brennan AM, Chamberland JP, Liu X, Fiorenza CG, Mylvaganam GH, Abanni L, Carbone F, Williams CJ, De Paoli AM, Schneider BE, Mantzoros CS. Efficacy of metreleptin in obese type II diabetics: cellular and molecular pathways underlying leptin tolerance. Diabetes. In press.
25. Mulligan K, Khatami H, Schwarz JM, Sakkas GK, DePaoli AM, Tai VW, Wen MJ, Lee GA, Grunfeld C, Schambelan M. The effects of recombinant human leptin on visceral fat, dyslipidemia, and insulin resistance in patients with human immunodeficiency virus-associated lipoatrophy and hypoleptinemia. J Clin Endocrinol Metab 94: 1137-1144, 2009.
26. Nakatani M, Kokubo M, Ohsawa Y, Sunada Y, Tsuchida K. Follistatin- derived peptide expression in muscle decreases adipose tissue mass and prevents hepatic steatosis. Am J Physiol Endocrinol Metab 300: E543-E553, 2011.
27. Rennie MJ, Wackerhage H, Spangenburg EE, Booth FW. Control of the size of the human muscle mass. Annu Rev Physiol 66: 799-828, 2004.
28. Sáinz N, Rodríguez A, Catalán V, Becerril S, Ramírez B, Gómez- Ambrosi J, Frühbeck G. Leptin administration favors muscle mass accretion by decreasing FoxO3a and increasing PGC-1alpha in ob/ob mice. PLoS One 4: e6808, 2009.
29. Schuelke M, Wagner KR, Stolz LE, Hubner C, Riebel T, Komen W, Braun T, Tobin JF, Lee SJ. Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med 350: 2682-2688, 2004.
30. Sood A. Sex differences: implications for the obesity-asthma association. Exerc Sport Sci Rev 39: 48-56, 2011.
31. Walker KS, Kambadur R, Sharma M, Smith HK. Resistance training alters plasma myostatin but not IGF-1 in healthy men. Med Sci Sports Exerc 36: 787-793, 2004.
32. Welt CK, Chan JL, Bullen J, Murphy R, Smith P, DePaoli AM, Karalis A, Mantzoros CS. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med 351: 987-997, 2004.
33. Yarasheski KE, Bhasin S, Sinha-Hikim I, Pak-Loduca J, Gonzalez- Cadavid NF. Serum myostatin-immunoreactive protein is increased in 60-92 year old women and men with muscle wasting. J Nutr Health Aging 6: 343-348, 2002.
34. Zimmers TA, Davies MV, Koniaris LG, Haynes P, Esquela AF, Tomkinson KN, McPherron AC, Wolfman NM, Lee SJ. Induction of cachexia in mice by systemically administered myostatin. Science 296: 1486-1488, 2002