Leptin: Defining its role in humans by the clinical study of genetic disorders

被引：21

作者：

O'Rahilly, S ^{[1
]}

机构：

[1] Addenbrookes Hosp, Cambridge Med Sch, Dept Med, Cambridge, England

来源：

NUTRITION REVIEWS | 2002年 / 60卷 / 10期

关键词：

homozygous mutations; leptin; hyperphagia; obesity; energy balance;

D O I：

10.1301/002966402320634904

中图分类号：

R15 [营养卫生、食品卫生]; TS201 [基础科学];

学科分类号：

100403 ;

摘要：

Extremely unusual genetic conditions can reveal normal processes governing physiologic regulation and metabolism. Children with rare homozygous mutations in the leptin gene and complete leptin deficiency develop extreme hyperphagia and obesity soon after birth but respond with normal eating and a selective loss of excess body fat upon being given small amounts of leptin. Heterozygote relatives have 30% more fat than predicted and relatively low leptin levels. This demonstrates leptin's fundamental involvement in maintaining energy balance. Leptin also seems to act as a metabolic gate allowing children to enter puberty.

引用

页码：S30 / S34

页数：5

共 13 条

[1] A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction [J].

Clément, K ;

Vaisse, C ;

Lahlou, N ;

Cabrol, S ;

Pelloux, V ;

Cassuto, D ;

Gourmelen, M ;

Dina, C ;

Chambaz, J ;

Lacorte, JM ;

Basdevant, A ;

Bougneres, P ;

Lebouc, Y ;

Froguel, P ;

Guy-Grand, B .

NATURE, 1998, 392 (6674) :398-401

[2] Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency [J].

Farooqi, IS ;

Yeo, GSH ;

Keogh, JM ;

Aminian, S ;

Jebb, SA ;

Butler, G ;

Cheetham, T ;

O'Rahilly, S .

JOURNAL OF CLINICAL INVESTIGATION, 2000, 106 (02) :271-279

[3] Effects of recombinant leptin therapy in a child with congenital leptin deficiency [J].

Farooqi, IS ;

Jebb, SA ;

Langmack, G ;

Lawrence, E ;

Cheetham, CH ;

Prentice, AM ;

Hughes, IA ;

McCamish, MA ;

O'Rahilly, S .

NEW ENGLAND JOURNAL OF MEDICINE, 1999, 341 (12) :879-884

[4] Metabolism - Partial leptin deficiency and human adiposity [J].

Farooqi, IS ;

Keogh, JM ;

Kamath, S ;

Jones, S ;

Gibson, WT ;

Trussell, R ;

Jebb, SA ;

Lip, GYH ;

O'Rahilly, S .

NATURE, 2001, 414 (6859) :34-35

[5] Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans [J].

Krude, H ;

Biebermann, H ;

Luck, W ;

Horn, R ;

Brabant, G ;

Grüters, A .

NATURE GENETICS, 1998, 19 (02) :155-157

[6] Molecular mechanisms of human hypertension [J].

Lifton, RP ;

Gharavi, AG ;

Geller, DS .

CELL, 2001, 104 (04) :545-556

[7] Congenital leptin deficiency is associated with severe early-onset obesity in humans [J].

Montague, CT ;

Farooqi, IS ;

Whitehead, JP ;

Soos, MA ;

Rau, H ;

Wareham, NJ ;

Sewter, CP ;

Digby, JE ;

Mohammed, SN ;

Hurst, JA ;

Cheetham, CH ;

Earley, AR ;

Barnett, AH ;

Prins, JB ;

ORahilly, S .

NATURE, 1997, 387 (6636) :903-908

[8] Truncated human leptin (Δ133) associated with extreme obesity undergoes proteasomal degradation after defective intracellular transport [J].

Rau, H ;

Reaves, BJ ;

O'Rahilly, S ;

Whitehead, JP .

ENDOCRINOLOGY, 1999, 140 (04) :1718-1723

[9] ESTROGEN RESISTANCE CAUSED BY A MUTATION IN THE ESTROGEN-RECEPTOR GENE IN A MAN [J].

SMITH, EP ;

BOYD, J ;

FRANK, GR ;

TAKAHASHI, H ;

COHEN, RM ;

SPECKER, B ;

WILLIAMS, TC ;

LUBAHN, DB ;

KORACH, KS .

NEW ENGLAND JOURNAL OF MEDICINE, 1994, 331 (16) :1056-1061

[10] A leptin missense mutation associated with hypogonadism and morbid obesity [J].

Strobel, A ;

Issad, T ;

Camoin, L ;

Ozata, M ;

Strosberg, AD .

NATURE GENETICS, 1998, 18 (03) :213-215

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