Page 36 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Obesity, Eating Disorders
Several regulatory circuits are considered to be there via MCR-4 receptors and has the oppo-
responsible for regulating body weight, each site effect of NPY.
governed by the hypothalamus, for example, Quite recently a homozygotic leptin receptor
by its ventromedial nucleus as the “satiety cen- defect was found in three very obese sisters. As
ter” and by the lateral hypothalamus as the they had never gone through puberty and the
“eating center”. The regulatory cycle that is secretion of both somatotropin hormone and
probably decisive in the long term is the lipo- thyrotropin-releasing hormone had been re-
static mechanism: the body’s fat mass is recog- duced, it seems that leptin also plays a part in
nized on the basis of a substance that is secret- other endocrine regulatory cycles.
ed by the fat cells (probably leptin, see below), In 90% of cases of eating disorders it is
and a feedback loop keeps this fat mass con- young women who are affected, bulimia ner-
stant during changes in appetite and physical vosa (bouts of overeating followed by self-in-
Temperature, Energy factor for hypertension, type 2 diabetes melli- duced weight loss through very restrictive
activity (→ A). Thus fat, even if surgically re-
duced vomiting and/or purgative abuse) being
more common than anorexia nervosa (self-in-
moved, is rapidly replaced.
Obesity (adiposity, excess weight) is a risk
diet). These eating disorders are characterized
by a distorted body self-image (the patients
tus, hyperlipidemia, atherosclerosis as well as
renal stones and gallstones. More than 40% ex-
feel “too fat” even though they have a normal
titude toward eating (association between the
premature death. Obesity is partly of (poly)ge-
netic, partly of environmental origin. Its causes
sense of one’s own worth and body weight).
2 cess weight is associated with a twofold risk of or below normal weight) and an abnormal at-
are little known. Two defective genes have There is a genetic disposition (50% concordance
been discovered, one in two male mouse in monozygotic twins), without the primary
strains with extreme obesity and one in type genetic defect being known. Psychological fac-
2 diabetes. If the ob[esity]-gene is defective, tors, such as disturbed family interaction
the 16-kDa protein leptin, coded by the ob- (overprotectiveness, avoidance of conflict, ri-
gene, is absent from plasma. Injection of leptin gidity) and sexual-pubertal conflicts as well
into mice with homozygotic ob mutation as socio-cultural influences (ideals of beauty,
counteracts the symptoms of the gene defect. social expectations) are probably significant.
Its administration to normal mice leads to The disorder in anorexia nervosa (→ B)
weight loss. But if the db-gene has mutated, ranges from eating a very restrictive diet to
the leptin receptor in the hypothalamus (in complete refusal to eat, and often includes
the arcuate nucleus, among other sites) is de- purgative abuse. This results in marked weight
fective. While high concentrations of leptin loss, even cachexia, which may require drip
circulate in plasma, the hypothalamus does feeding. It leads to severe autonomic–hormon-
not respond to them. Some obese persons also al disorders, for example, increased cortisol
have a defective leptin gene, but in most others and diminished gonadotropin release (amen-
the plasma leptin concentration is high. In this orrhea; loss of libido, and impotence in males),
case the feedback chain after leptin must have and even hypothermia, bradycardia, hair loss,
been interrupted somewhere (→ A, red X). Var- etc. If the condition takes a prolonged course,
ious possible defects have been postulated: the mortality rate can be up to 20%.
! Leptin can no longer overcome the blood– Bulimia is characterized by eating binges fol-
brain barrier (? defective transcytosis). lowed by self-induced vomiting; a reasonably
! The inhibitory effect of leptin on the secre- normal body weight may be maintained.
tion of neuropeptide Y (NPY) in the hypothal-
amus, which stimulates food intake and re-
duces energy consumption, is abnormal.
! Leptin does not cause the release in the hy-
26 pothalamus of α-melanocortin (melanocyte-
stimulating hormone [α-MSH]), which acts
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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