Function of leptin:-The hormones which
causes anorexia and thereby prevents overeating. The balancing hormones.
Leptin after being secreted by white
fact cells acts on receptors in the hypothalamus of the brain where it A) inhibits
appetite by counteracting the
effects of neuropeptide Y (a potent feeding stimulant secreted by cells in the gut
and in the hypothalamus); B) counteracts the effects of anandamide (another potent
feeding stimulant that binds to the same receptors as THC, the primary active ingredient of marijuana); and C) promoting
the synthesis of α-MSH, an
appetite suppressant.
Correlation between
Melatonin(sleep hormones) with secretion of Leptin:--There is some controversy regarding the regulation of
leptin by melatonin during the night. It
has been suggested that increased
levels of melatonin caused a downregulation
of leptin.. Brazilian researchers found that melatonin increases leptin levels in
the presence of insulin,
therefore causing a decrease in appetite during sleeping.
Can we treat DM with insulin & Leptin
as adjunct?? Possibly yes. Mice
with type 1 diabetes treated with leptin alone or in conjunction with insulin
did better (blood sugar did not fluctuate as much; cholesterol levels
decreased; mice formed less body fat) than mice with type 1 diabetes treated
with insulin alone, raising the prospect of a new treatment for diabetes. But unfortunately
However, extensive clinical trials using recombinant human leptin as a
therapeutic agent for treating obesity in humans have been inconclusive because
only the most obese subjects who were given the highest doses of exogenous
leptin produced statistically significant weight loss. These problems (less
efficacy of r-leptincan ) was alleviated by a form of leptin called Fc-leptin, which takes the Fc fragment from the
immunoglobulin gamma chain as the N-terminal fusion partner and follows it with
leptin. This Fc-leptin fusion has been
experimentally proven to be highly soluble, more biologically potent, and
contain a much longer serum half-life
Adiposity signal & Adiposity amount is governed by two main hormones
of body :-To date, only leptin and insulin are known to act as an adiposity signal. Though theoretically appetite is controlled by many other
hormones & growth factors e .like TSH, ACTH, NPY (Neurotransmitter-Neuropeptide-Y-e,g. in short called NPY
. In practice, ,Leptin circulates at levels proportional to body fat.
controls food intake and energy expenditure by acting on receptors in the
mediobasal hypothalamus.. Circulating leptin levels give the brain input regarding
energy storage so it can regulate appetite and metabolism. Leptin works by inhibiting the activity of neurons that contain neuropeptide Y (NPY) and agouti-related peptide (AgRP), and by increasing the activity of neurons expressing α-melanocyte-stimulating hormone (α-MSH). The NPY neurons are a key element in the
regulation of appetite; small doses of NPY injected into the brains of
experimental animals stimulates feeding, while selective destruction of the NPY
neurons in mice causes them to become anorexic.
Conversely, α-MSH is an important mediator of satiety, and differences in the gene for the receptor at which α-MSH acts in the brain are
linked to obesity in humans. To summarize:-
·
Leptin receptors are found in brain neurons involved
in regulating energy intake
and expenditure.What happens in PCO: There is high leptin ,So such elevated
leptin concentrations are associated with elevated white blood cell counts. Similar
to what is observed in chronic inflammation, chronically-elevated leptin levels
as happens in PCO are associated with more obesity, more overeating, and
inflammation-related diseases including hypertension&
metabolic syndrome.
research suggests that hypothalamic leptin is
implicated in bone growth. A number of theories have been put forward
concerning the cortical-cancellous dichotomy including a recent theory
suggesting that increased leptin during obesity may represent a mechanism for
enlarging bone size and thus bone resistance to cope with increased body weight.
What is amylin-- produced by beta cells in the pancreas) and leptin
(produced by fat cells?? 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 leptin-resistant animal model of obesity.
What controls Satiety??
How leptin prevents
overeating??? How it minimizes overeating?? The dynamics?? 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.
A very small group of humans possess homozygous mutations
for the leptin gene that leads to a constant desire for food, resulting in
severe obesity. This condition can be treated
somewhat successfully by the administration of recombinant human leptin. A
number of brain signalling molecules (neuropeptides and neurotransmitters) have been found in bone including adrenaline, noradrenaline, serotonin, calcitonin gene-related peptide, vasoactive intestinal peptide and neuropeptide Y.[33][34] This evidence supports a direct signalling system between
the brain and bone with accumulating evidence suggesting that these molecules
are directly involved in the regulation of bone metabolism. Leptin, once
released from fat tissue, can cross the blood-brain barrier and bind to its receptors in the brain where it acts
through the sympathetic nervous system to regulate bone metabolism.It is also possible that, in
addition to its effects through the brain, leptin may act directly on cells in
the bone to regulate bone metabolism. In reality, leptin probably signals to
bone on multiple levels, with local and systemic checks and balances impacting
the final outcome. As a result, the clinical utility of leptin for treatment of
bone diseases remains open but ongoing research may yet provide much needed
therapies for stimulating bone formation.
Circulatory system & leptin:-The role of leptin/leptin receptors
in modulation of T cell activity in immune system was shown in experimentation with
mice. It modulates the immune response to atherosclerosis, which is a
predisposing factor in patients with obesity.eptin promotes angiogenesis by increasing vascular endothelial growth factor (VEGF) levels.In some epidemiological studies,
hyperleptinemia is considered as a risk factor. However, recently a handful of
animal experiments demonstrated that systemic hyperleptinemia produced by
infusion or adenoviral gene transfer decrease blood pressure in rats.
Lung surfactant activity
In fetal lung leptin is induced in the alveolar
interstitial fibroblasts ("lipofibroblasts") by the action of PTHrP secreted by formative alveolar epithelium
(endoderm) under moderate stretch. The leptin from the mesenchyme, in turn,
acts back on the epithelium at the leptin receptor carried in the alveolar type
II pneumocytes and induces surfactant expression, which is one of the main
functions of these type II pneumocytes.
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