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Effects of Leptin on Exercise
and Health in Human
Human Leptin
A protein of 167 amino acids.
A molecular weight of 16 kDa, peptide
hormone secreted by adipose tissue.
the level in circulation is directly proportional
to the total amount of fat in the body.
regulates body weight and energy homeostasis
via its actions on specific hypothalamic nuclei
Biosynthesis
the major source of leptin:
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brown adipose tissue,
placenta (syncytiotrophoblasts),
ovaries, skeletal muscle,
stomach (lower part of fundic glands),
mammary epithelial cells,
bone marrow,
Pituitary
and liver
Leptin has also been discovered to be synthesised
from gastric chief cells and P/D1 cells in the stomach
Leptin Production and Adipocyte
Biosynthesis
Leptin is the product of the obese (ob) gene
that is synthesized predominantly, although not
exclusively, by white adipose tissue
The Ob(Lep) gene (Ob for obese, Lep for
leptin) is located on chromosome 7 (q31.31q32.1) in humans.
Function
Leptin acts on receptors in the hypothalamus of
the brain where it inhibits appetite by
– (1) counteracting the effects of neuropeptide Y (a
potent feeding stimulant secreted by cells in the gut
and in the hypothalamus);
– (2) counteracting the effects of anandamide (another
potent feeding stimulant that binds to the same
receptors as THC, the primary active ingredient of
marijuana);
– (3) promoting the synthesis of α-MSH, an appetite
suppressant
Satiety
Leptin binds to neuropeptide Y (NPY) neurons
in the arcuate nucleus, in such a way that
decreases the activity of these neurons.
Leptin signals to the brain that the body has
had enough to eat, producing a feeling of
satiety
Regulation of satiety signals
Model for regulation of the hindbrain response
to satiety signals by hormonal input from the
ARC.
Adiposity signals such as insulin and leptin
circulate in proportion to body fat mass and act
on hypothalamic ARC neurons that project to
hypothalamic areas such as the PVN
these “second order” neurons project to
hindbrain autonomic centers such as the NTS
that process afferent input from satiety signals
such as CCK.
Input from descending, leptin-sensitive
hypothalamic projections is integrated in the
NTS with vagally mediated input from CCK,
such that the timing of meal termination is
regulated by changes in body fat content
Interaction with amylin
Co-administration of two neurohormones
known to have a role in body weight control,
amylin (produced by beta cells in the pancreas)
and leptin (produced by fat cells), results in
sustained, fat-specific weight loss in a leptinresistant animal model of obesity
Leptin and Obesity
obese individuals generally
exhibit an unusually high
circulating concentration of
leptin
the high sustained
concentrations of leptin from
the enlarged adipose stores
result in leptin desensitization
The pathway of leptin
control in obese people
doesn't adequately receive
the satiety feeling subsequent
to eating
As it circulates through the cerebrovasculature,
transporters for leptin carry it across the BBB
to enter the interstitial fluid of the brain
Leptin functions are thought to occur through
the leptin receptors mainly in the hypothalamic
nuclei
Model of leptin regulation of NPY/GABA and POMC neurons in the ARC
Function
Leptin acts on receptors in the hypothalamus of
the brain where it inhibits appetite by
– (1) counteracting the effects of neuropeptide Y(a
potent feeding stimulant secreted by cells in the gut
and in the hypothalamus);
– (2) counteracting the effects of anandamide (another
potent feeding stimulant that binds to the same
receptors as THC, the primary active ingredient of
marijuana);
– (3) promoting the synthesis of α-MSH, an appetite
suppressant
This inhibition is long-term, in contrast to the
rapid inhibition of eating by cholecystokinin
(CCK) and the slower suppression of hunger
between meals mediated by PYY3-36.
Peptide YY3-36 (PYY3-36), a Y2R agonist, is
released from the gastrointestinal tract
postprandially in proportion to the calorie content
of a meal
Presynaptic Inhibition
The absence of leptin (or its receptor) leads to
uncontrolled food intake and resulting obesity.
Several studies have shown that fasting or
following a very-low-calorie diet (VLCD)
lowers leptin levels
Dynamics of leptin due to an acute change in
energy balance are related to appetite and
eventually to food intake
Two neurohormones known to have a role in
body weight control, amylin (produced by beta
cells in the pancreas) and leptin (produced by
fat cells),
Resting leptin responses to acute and chronic
resistance training in type 2 diabetic men and
women.
17 controls and 13 type 2, obese diabetics, age
40-55 y
resting blood samples drawn at 08:00 h (12 h
postprandial) at the beginning of the study
(pre-training)
24 h after a three repetition maximal weight
lifting bout (acute) and 72 h after their last
training bout of 6 weeks of resistance training
(chronic)
Kanaley JA, Fenicchia LM, Miller CS, Ploutz-Synder LL, Weinstock RS, Carhart R, Azevedo JL Jr.Int J Obes Relat Metab Disord.
2001 Oct;25(10):1474-80.
Serum leptin concentrations were significantly
higher in the type 2 diabetics than in the
control group at pre-training
Compared to pre-training, the leptin levels
decreased after acute exercise in the diabetics
but not in the control subjects
The decreased resting leptin concentrations
approximately 24 h post-acute exercise may be
due to reduced glucose availability to the
adipose tissue
Leptin concentrations experience a delayed
reduction after resistance exercise in men.
Nindl BC, Kraemer WJ, Arciero PJ, Samatallee N, Leone CD, Mayo MF, Hafeman D
Ten men completed an acute heavy-resistance
exercise protocol (AHREP;50 total sets comprised of
the squat, bench press, leg press, and lat pull-down)
from 1500 to 1700 h.
Blood was sampled hourly postexercise until 0600 h
the next morning and also during a time-matched
control period.
Leptin concentrations were measured by an
immunoradiometric assay.
Resting energy expenditure (REE) was measured via
indirect calorimetry using a ventilated hood
beginning approximately 0600 h after both overnight
conditions.
The estimated caloric expenditure from the
AHREP was 856 +/- 114 kcal.
No differences between the control and
exercise conditions were observed for serum
leptin concentrations until 9 h postexercise.
Significant interaction effects indicated lower
serum leptin concentrations postexercise at
hours 9, 10, 12 , and 13 .
This delayed reduction was accompanied by a
12% elevation in morning-after REE
Leptin concentrations experience a delayed
( approximately 9 h) reduction in the systemic
circulation after acute resistance exercise. This
decline is likely associated with the disruption
in metabolic homeostasis created by the highintensity, long-duration, energy expenditure
Summary
Leptin circulates at levels proportional to body
fat.
It enters the central nervous system (CNS) in
proportion to its plasma concentration.
Its receptors are found in brain neurons
involved in regulating energy intake and
expenditure.
It controls food intake and energy expenditure
by acting on receptors in the mediobasal
hypothalamus
Response of leptin to muscular exercise.
Physical exercise and or training can reduce fat
mass
Changes in energy expenditure and affect
hormonal concentrations (insulin, cortisol,
growth hormone, catecholamines, testosterone
etc.) and
metabolites (free fatty acids, lactic acid,
triglycerides etc.).
Discussion
What is your thinking about the relation
between the human leptin and athletic
performance?
Could you draw a diagram to denote the
leptid’s effect on POMC/CART and
NPY/AgRP and Arcuate nucleus to change an
eating behavior.
gut peptide cholecystokinin (CCK)
hypothalamic arcuate nucleus (ARC) a key forebrain site of leptin action
agouti-related peptide (AgRP),
α-melanocyte-stimulating hormone (α-MSH).
Pro-opiomelanocortin (POMC)
Cocaine-and amphetamine-regulating transcrip (CART)
Ghrelin, a hormone secreted when stomach is empty
Peptide YY 3-36 (PYY3-36) is produced by the gut
and is released into the circulation in response to food ingestion
Y2R agonist is peptide YY3 36 (PYY3 36),