Page 243 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

Energy Homeostasis and Body Weight Effects of leptin. In contrast to primary star-
vation, the weight loss induced by leptin is re-
Fat depots are by far the body’s largest energy stricted to the body’s fat depots and completes
reserve. Accurate long-term homeostasis of the feedback loop of the regulatory process.
energy absorption and consumption is neces- The effects of leptin are chiefly mediated by
sary to keep the size of the fat depots constant, two neurotransmitters located in the hy-
i.e., to maintain lipostasis. Considering that a pothalamus: α-MSH and NPY (! B).
person’s body weight (BW) mainly varying ! α-MSH. Leptin stimulates the release of α-
with the weight of the fat depots, it is obvious MSH (α-melanocyte-stimulating hormone),
that energy homeostasis is synonymous with one of the melanocortins (MC) synthesized
the regulation of body weight (! A). from POMC (! p. 280). α-MSH inhibits the ab-
The body mass index (BMI) is commonly sorption of nutrients and increases sympa-
Nutrition and Digestion in men. The “normal” BMI range is defined as the hypothalamus.
used to determine whether an individual is
thetic nervous activity and energy consump-
tion via MC4 receptors in various areas of the
underweight, overweight or in the normal
weight range. BMI is calculated from body
weight (kg) and height (m) as follows:
The mechanism by which α-MSH increases energy
2
[10.3]
BMI = (weight/height)
consumption is not entirely clear, but an involuntary
increase in ordinary skeletal muscle activity and tone
The normal BMI range is 19–24 in women and 20–25
appears to occur. In addition, uncoupling proteins
values at which the mean life expectancy is highest.
in skeletal muscle and white fat make the mem-
An abnormally high body mass index (BMI ! 24 or 25
+
branes of the mitochondria more permeable to H ,
10 = overweight; BMI ! 30 = obesity) reduces the life (type UCP2 and UCP3) that were recently discovered
thereby uncoupling the respiratory chain. As a result,
expectancy since this is often associated with dia-
betes mellitus (type II), hypertension and cardiac dis- chemical energy is converted into more heat and less
ease. ATP. The action of these UCPs, the expression of
which may be stimulated by α-MSH, is therefore sim-
The following regulatory mechanisms serve to ilar to that of thermogenin (UCP1; ! p. 222).
keep the fat depots and thus the body weight ! NPY. Leptin inhibits the hypothalamic re-
constant (! B):
! The hypothalamus, the center responsible lease of NPY (neuropeptide Y), a neuropeptide
for feedback control of BW, maintains com- that stimulates hunger and appetite, increases
the parasympathetic activity and reduces
munication with the limbic system, cerebral energy consumption.
cortex and brain stem. It sends and receives:
! Afferent messages concerning the size of fat Leptin deficiency. Since NPY increases the secretion
depots. Leptin, a 16-kDa proteohormone pro- of gonadotropin-releasing hormone (GnRH), ex-
duced by fat cells, is the main indicator for this. treme weight loss results in amenorrhea (! B). Cer-
The plasma leptin concentration rises as fat tain genetic defects can lead to impaired leptin pro-
cell mass increases. duction (ob [obesity] gene) or impaired leptin recep-
tor function (db [diabetes] gene). The symptoms in-
! Efferent commands (a) to reduce nutrient clude arrested development in puberty and child-
absorption and increase energy consumption hood obesity.
when plasma leptin are high (“fat reserve Other neurotransmitters and neuropeptides also
high!”), and (b) to increase nutrient absorption play a role in the long-term regulation of fat depots.
and decrease energy consumption when Some like orexin A/B and norepinephrine (α 2-adreno-
plasma leptin levels are low (“fat reserve ceptors) are orexigenic, i.e. they stimulate the ap-
low!”) (! B). petite, while others like CCK, CRH, CART (cocaine
and amphetamine-regulated transcript), insulin, and
Leptin receptors. Leptin binds with type b serotonin are anorexigenic. Peptides like CCK, GLP-
leptin receptors (Ob-Rb) of the hypothalamus 1 (glucagon-like peptide amides), somatostatin,
(mainly in dorsomedial, ventromedial, lateral, glucagon, and GRP (gastrin-releasing peptide) signal
paraventricular and arcuate nuclei). Certain satiety, i.e., that one has had enough to eat. Together
neurons with Ob-Rb lie in front of the blood– with gustatory stimuli and stretch receptors of the
brain barrier. (T lymphocytes and B cells of the stomach wall, these satiety peptides help to limit
230 the amount of food consumed with each meal.
pancreas are also equipped with Ob-Rb recep-
tors.)
Despopoulos, Color Atlas of Physiology © 2003 Thieme
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