Applications
In Brief
References
Alzheimer’s
Leptin benefits the functional characteristics and viability of
neurons that degenerate in AD. Leptin protects cortical neurons
from AB(1-42) and promotes tau clearance.
(1) Leptin receptors have been detected on human platelets.
Leptin at high serum (blood) concentrations corresponding to those
of obese individuals was found to act synergistically with ADP to
promote platelet aggregation – a component of atherosclerosis and
cardiovascular disease.
Leptin appears to activate multiple cell signaling pathways within
the cell. Thus, activities such as: (1) protection against oxidative
stress, (2) loss of dopamine neurons, and (3) cognitive (behavior,
learning, memory) function are all influenced by leptin.
(1) In laboratory research with rodents, leptin has been reported to
normalize blood sugar and inhibit insulin secretion when added to
the culture of isolated pancreatic islet cells. Leptin has been
shown to inhibit the insulin-stimulated synthesis of fatty acids and
total lipids.
(1) Leptin protects hippocampal neurons against cell death induced
by epilepsy.
Doherty GH et al. Leptin prevents hippocampal
synaptic disruption and neuronal cell death
induced by amyloid B. Neurobiol. Aging.
2013(Jan);34(1):226-237.
(1) Nakata M, Yada T, Soejima N, Maruyama I.
Leptin promotes aggregation of human platelets
via the long form of its receptor. Diabetes. 1999
Feb;48:426-429.
Atherosclerosis
Cognitive
Impairment
Diabetes
Mellitus I & II
Epilepsy
Arteriogenic
Erectile
Dysfunction
Pluripotent
Hormonal
Influences
Hypertension
A-ED is caused by an impaired ability of blood vessels to open and
allow a normal blood flow; obesity is a major contributing factor.
Excess serum leptin might be related to plaque build-up in blood
vessels, thereby restricting flow.
Leptin plays a significant permissive role in the physiological
regulation of several neuroendocrine axes, including the
hypothalamic-pituitary-gonadal, thyroid, growth hormone, and
adrenal axes.
(1) One of the peripheral functions of leptin includes the regulation
of blood pressure via endothelial cells.
(2) Leptin infusion was shown to reduce blood pressure and heart
rate, and to stimulate NO in the cardiovascular system.
Infertility
Leptin may be of importance in obesity-associated dysfunction of
the reproduction system. It is possible that leptin acts on the
reproductive system both at the hypothalamic-pituitary level
(GnRH-FSH/LH) and directly on the ovary.
Insomnia
Short sleep duration has been found to be related to metabolic
disorders such as obesity, metabolic syndrome and type 2
diabetes, and insulin resistance, which are all influenced by leptin.
(1) Leptin improves insulin sensitivity, and decreases insulin
secretion by potentiating hypothalamic leptin and insulin signaling
by stimulating IRS2 phosphorylation.
This sets up a stimulating/inhibiting feedback loop between leptin
and insulin. Data from research studies support the hypothesis
that leptin may exert direct action on insulin resistance, insulin
secretion, insulin hepatic extraction, and insulin delivery.
Leptin influences all aspect of MS: (1) visceral adipose tissue –
central obesity, (2) hyperlipidemia – raised triglyceride levels, (3)
insulin resistance – raised fasting glucose levels, (4) hypertension.
(5) reduced HDL cholesterol, and (6) increased blood pressure.
Adipocytes and osteoblasts are derived from a common
multipotential mesenchymal stem cells. Excess obesity-associated
leptin may increase adipocyte differentiation and fat accumulation
while decrease osteoblast differentiation and bone formation.
(1) Leptin can reverse dopaminergic cell loss and functional
behaviors via the MEK/ERK signaling pathway.
Insulin
Resistance
Metabolic
Syndrome
Osteoporosis
Parkinson’s
Premature
Puberty
Leptin serves as the adipose-brain signal for the onset of sexual
maturation. Leptin influences FSH and IGF-1 stimulated
progesterone production.
Visit www.LepticaResearch.com for more information.
Morrison CD, Leptin signaling in brain: a link
between nutrition and cognition? Biochim
Biophys Acta. 2009 May;1972(5):401-408.
(1) Emilsson V, Liu YI et al.Expression of the
functional leptin receptor mRNA in pancreatic
islets and direct inhibitory action of leptin on
insulin secretion. Diabetes. 1997;46:313-316.
(1) Diano S, Horvath TL, Anticonvulsant effects
of leptin in epilepsy. J Clin. Invest. 2008;118:2628.
Dozio E, et.al, Adipokines, hormonal parameters
and cardiovascular risk factors: similarities and
differences between patients with erectile
dysfunction of arteriogenic and nonarteriogenic
origin. J Sex Med. 2012(Sep);9(9):2370-2377.
Khan, SM, Hamnvik OR, et al. Leptin as a
modulator of neuroendocrine function in
humans. Yonsei Medical Journal, 2012
(Jul);53(4):671-679.
(1) Lembo G, Vecchione C, Leptin induces direct
vasodilation through distinct endothelial
mechanisms. Diabetes. 2000;49:293-297.
(2) Fruhbeck G, Pivotal role of nitric oxide in the
control of blood pressure after leptin
administration. Diabetes. 1999;48:903-908.
Zachow RJ, Magoffin DA. Direct intraovarian
effects of leptin: impairment of the synergistic
action of insulin-like growth factor-1 on follicle
stimulating hormone-dependent estradiol-17B
production by rat ovarian granulosa cells.
Endocrinology. 1997;138:847-850.
Reynolds AC, Dorrian J, et al. Impact of five
nights of sleep restriction on glucose
metabolism, leptin and testosterone in young
adult men. PLos One, 2012(Jul);7(7):1-10.
(1) Park SM, Hong SM, Sung SR, Jung HK.
Long-term effects of central leptin and resistin
on body weight, insulin resistance, and β-cell
function and mass by the modulation of
hypothalamic leptin and insulin signaling.
Endocrinology. 2008;149(2):445-454.
Bae YJ, Kim SH, et.al., Evaluation of adiposityrelated biomarkers as metabolic syndrome
indicators. Clin Nutri Res. 2013;2:91-99.
Cao JJ, Effects of obesity on bone metabolism.
J Orthop Surg Res. 2011 (Jun); 6(30):
(1) Weng ZF, Signore AP et.al, Leptin protects
against 6-hydroxydopamine-induced
dopaminergic cell death via mitogen-activated
protein kinase signaling. J of Biol Chem. 2007
(Nov); 282 (47): 34479-34491.
Mantzoros CS, et al. A longitudinal assessment
of hormonal and physical alterations during
normal puberty in boys. Rising leptin levels may
signal the onset of puberty. J Clin Endocrinol
Metab. 1997;82:1266-1070.