Leptin applications in 2015: what have we learned about leptin and obesity?

被引:173
作者
Farr, Olivia M.
Gavrieli, Anna
Mantzoros, Christos S.
机构
[1] Harvard Univ, Sch Med, Div Endocrinol, Boston VA Healthcare Syst, Boston, MA USA
[2] Harvard Univ, Beth Israel Deaconess Med Ctr, Endocrinol Sect, Sch Med, Boston, MA 02215 USA
关键词
hypoleptinemia; leptin; leptin resistance; lipodystrophy; obesity; REVERSES INSULIN-RESISTANCE; EARLY-ONSET OBESITY; FUNCTIONAL HYPOTHALAMIC AMENORRHEA; FAMILIAL PARTIAL LIPODYSTROPHY; LONG-TERM EFFICACY; REPLACEMENT THERAPY; WEIGHT-LOSS; GENERALIZED LIPODYSTROPHY; METABOLIC ADAPTATION; ANOREXIA-NERVOSA;
D O I
10.1097/MED.0000000000000184
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Purpose of reviewTo summarize previous and current advancements for leptin therapeutics, we described how leptin may be useful in leptin deficient states such as lipodystrophy, for which leptin was recently approved, and how it may be useful in the future for typical obesity.Recent findingsThe discovery of leptin in 1994 built the foundation for understanding the pathophysiology and treatment of obesity. Leptin therapy reverses morbid obesity related to congenital leptin deficiency and appears to possibly treat lipodystrophy, a finding which has led to the approval of leptin for the treatment of lipodystrophy in the USA and Japan. Typical obesity, on the other hand, is characterized by hyperleptinemia and leptin tolerance. Thus, leptin administration has proven ineffective for inducing weight loss on its own but could possibly be useful in combination with other therapies or for weight loss maintenance.SummaryLeptin is not able to treat typical obesity; however, it is effective for reversing leptin deficiency-induced obesity and is possibly useful in lipodystrophy. New mechanisms and pathways involved in leptin resistance are continuously discovered, whereas the development of new techniques and drug combinations which may improve leptin's efficacy and safety regenerate the hope for its use as an effective treatment for typical obesity.
引用
收藏
页码:353 / 359
页数:7
相关论文
共 104 条
[1]   Pharmacokinetics of human leptin in mice and rhesus monkeys [J].
Ahrén, B ;
Baldwin, RM ;
Havel, PJ .
INTERNATIONAL JOURNAL OF OBESITY, 2000, 24 (12) :1579-1585
[2]   Functional Magnetic Resonance Imaging Analysis of Food-Related Brain Activity in Patients with Lipodystrophy Undergoing Leptin Replacement Therapy [J].
Aotani, Daisuke ;
Ebihara, Ken ;
Sawamoto, Nobukatsu ;
Kusakabe, Toru ;
Aizawa-Abe, Megumi ;
Kataoka, Sachiko ;
Sakai, Takeru ;
Iogawa, Hitomi ;
Ebihara, Chihiro ;
Fujikura, Junji ;
Hosoda, Kiminori ;
Fukuyama, Hidenao ;
Nakao, Kazuwa .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2012, 97 (10) :3663-3671
[3]   Preadipocyte Factor-1 Levels Are Higher in Women with Hypothalamic Amenorrhea and Are Associated with Bone Mineral Content and Bone Mineral Density through a Mechanism Independent of Leptin [J].
Aronis, Konstantinos N. ;
Kilim, Holly ;
Chamberland, John P. ;
Breggia, Anne ;
Rosen, Clifford ;
Mantzoros, Christos S. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2011, 96 (10) :E1634-E1639
[4]   Leptin in relation to resumption of menses in women with anorexia nervosa [J].
Audi, L ;
Mantzoros, CS ;
Vidal-Puig, A ;
Vargas, D ;
Gussinye, M ;
Carrascosa, A .
MOLECULAR PSYCHIATRY, 1998, 3 (06) :544-547
[5]   Leptin replacement alters brain response to food cues in genetically leptin-deficient adults [J].
Baicy, Kate ;
London, Edythe D. ;
Monterosso, John ;
Wong, Ma-Li ;
Delibasi, Tuncay ;
Sharma, Anil ;
Licinio, Julio .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (46) :18276-18279
[6]   Role of the blood-brain barrier in the evolution of feeding and cognition [J].
Banks, William A. .
BRAIN AND OBESITY, 2012, 1264 :13-19
[7]   Metabolic correction induced by leptin replacement treatment in young children with Berardinelli-Seip congenital lipoatrophy [J].
Beltrand, Jacques ;
Beregszaszi, Marta ;
Chevenne, Didier ;
Sebag, Guy ;
De Kerdanet, Marc ;
Huet, Frederic ;
Polak, Michel ;
Tubiana-Rufi, Nadia ;
Lacombe, Didier ;
De Paoli, Alex M. ;
Levy-Marchal, Claire .
PEDIATRICS, 2007, 120 (02) :E291-E296
[8]   Resistance to leptin-replacement therapy in Berardinelli-Seip congenital lipodystrophy: an immunological origin [J].
Beltrand, Jacques ;
Lahlou, Najiba ;
Le Charpentier, Tifenn ;
Sebag, Guy ;
Leka, Sofia ;
Polak, Michel ;
Tubiana-Rufi, Nadia ;
Lacombe, Didier ;
de Kerdanet, Marc ;
Huet, Frederic ;
Robert, Jean-Jacques ;
Chevenne, Didier ;
Gressens, Pierre ;
Levy-Marchal, Claire .
EUROPEAN JOURNAL OF ENDOCRINOLOGY, 2010, 162 (06) :1083-1091
[9]   ALTERED NEUROANATOMICAL ORGANIZATION IN THE CENTRAL NERVOUS-SYSTEM OF THE GENETICALLY-OBESE (OB-OB) MOUSE [J].
BEREITER, DA ;
JEANRENAUD, B .
BRAIN RESEARCH, 1979, 165 (02) :249-260
[10]   Women with functional hypothalamic amenorrhea but not other forms of anovulation display amplified cortisol concentrations [J].
Berga, SL ;
Daniels, TL ;
Giles, DE .
FERTILITY AND STERILITY, 1997, 67 (06) :1024-1030