chapter 5
Thermodynamics, Chemical Kinetics, and Energy Metabolism
births). Deletions in chromosome 15 account for a ma-
jority of cases of Prader-Willi syndrome. In other cases,
a novel genetic mechanism of uniparental disomy is the
cause of this syndrome. Congenital human leptin defi-
ciency is associated with early-onset obesity. Homozygous
mutations in the human leptin receptor gene result in a
truncated leptin receptor lacking both transmembrane and
intracellular domains; such mutations are associated with
early-onset obesity, absence of pubertal development, and
pituitary dysfunction.
In most obese humans, the plasma levels of leptin are
high due to excess adipose tissue. In spite of abundant lep-
tin, there is continued overeating. This puzzling observa-
tion may ultimately be explained by as yet-to-be identified
defects in leptin metabolism.
Supplemental Readings and References
P. Bjorntorp: Obesity.
L a n c e t
423 (1997).
J. F. Caro, J. W. Kolaczynski, M. R. Nyce, et al.: Decreased cerebrospinal -
fluid/serum leptin ratio in obesity: A possible mechanism for leptin resis-
L a n cet
348, 159 (1996).
K. Clement, C. Vaisse, N. Lahlou, et at: A mutation in the human leptin
receptor gene causes obesity and pituitary dysfunction.
N a tu re
J. M. Friedman and J. L. Halaas: Leptin and the regulation of body weight
in mammals.
N a tu re
763 (1998).
C. T. Montague, I. S. Farooqi, J. P. Whitehead, et at: Congenital leptin
deficiency is associated with severe early-onset obesity in humans.
N a tu re
J. E. Morley: Anorexia of aging: Physiologic and pathologic.
A m erica n
J o u rn a l o f C lin ica l N u tritio n
, 760 (1997).
R ec o m m en d e d D ieta ry A llo w a n c e s,
10th ed. Food and Nutrition Board,
National Research Council-National Academy of Sciences, Washington,
DC, (1989).
M. Rosenbaum, R. L. Liebel, and J. Hirsch: Obesity.
N ew E n g la n d Jo u rn a l
o f M ed icin e
396 (1997).
M. W. Schwartz, E. Peskind, M. Raskind, et al.: Cerebrospinal fluid leptin
levels: Relationship to plasma levels and to adiposity in humans.
N ature
M ed icin e
2 ,
589 (1996).
J. Stevens, J. Cai, E. R. Parnuk, et al.: The effect of age on the association be-
tween body-mass index and mortality.
N ew E n g la n d J o u rn a l o f M ed icin e
L. A. Tartaglia, M. Dembroski, X. Weng, et al.: Identification and
expression of cloning of a leptin receptor, OB-R.
C ell
R. Weindruch and R. S. Sohal: Caloric intake and aging.
N ew Jo u rn a l o f
M ed icin e
previous page 114 Bhagavan Medical Biochemistry 2001 read online next page 116 Bhagavan Medical Biochemistry 2001 read online Home Toggle text on/off