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LEPTIN
Going for the 3 Increases: Increase in Health, Increase in
Happiness & Increase in Energy
Strategies for
Success in Weight
Management
By: James J. Messina, Ph.D.
What is Leptin
About fifty years ago genetic mutation
was discovered which causes massive
obesity in mice
 In 1994 mutation was characterized as
an inactivation of a specific gene product
 Gene product was subsequently termed
leptin (from Greek for low-weight)
because when product was injected into
mice they lost weight

Leptin System:
What is Leptin?
Leptin was found to be produced in fat
cells, so amount of leptin in blood is
generally proportional to weight of person
 Since absence of leptin causes obesity &
leptin itself reduces body fat, it was
hypothesized that physiological function
of leptin was to serve as a reporter of
degree of body fat

What is Leptin?
Broad outlines of physiologic circuit of
appetite regulation & energy expenditure
regulated by leptin have been mapped
 Leptin levels rise in proportion to adiposity
(fat cells) but at any given level of adipose
there is wide variability in concentration of
plasma leptin
 Leptin levels are elevated in persons with
obesity & insulin resistance

What research has told us about
Leptin

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It was quickly apparent that leptin is generally
ineffective as signal for excessive body fat, since
obese people generally have higher, not lower,
levels of leptin, but yet remain obese
Probably more important role of leptin is to signal
to body that body fat has fallen to dangerously low
levels (for example during starvation) & thus
signal that appropriate metabolic changes should
occur to preserve metabolic resources. This
current view of leptin was supported by the results
of clinical trials of leptin on overweight individuals.
What research has told us about
Leptin
Over 200 candidate genes for obesity-most
remain unidentified in humans
 Considerable amount of research has
focused on hypothetical link between
obesity & type 2 diabetes in region of leptin
receptor gene
 But sequence variations that have been
detected have not yet been linked to body
fat mass

What we know about Leptin


Women have higher leptin levels than men,
even after accounting for estrogen status (e.g.,
there are no consistent differences among
premenopausal women, postmenopausal
women, and postmenopausal women on
estrogen replacement)
There is a possibility that testosterone in men
might have a suppressive effect on production
of leptin by the adipocyte
What we know about Leptin- A key
factor is body energy status



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Short-term energy restriction leads to a marked
fall in circulating leptin levels, even after adjusting
for changes in adipose mass
Fall is associated with increased hunger, which
may be an early impediment to compliance with a
low-energy diet to achieve weight loss
While a number of potential signals could
mediate the acute fall in leptin with energy
restriction
Plasma insulin concentrations decline in parallel
with leptin levels in this condition
What we know about Leptin-Dietary
Composition
Dietary composition can affect leptin
production by the adipocyte
 High-fat diet reduces leptin levels more
than a high-carbohydrate diet does
 Fructose reduces leptin levels more than
glucose does
 These findings have obvious implications
for the relation of dietary compositionspecifically high-fat diets-to weight gain

How does Leptin work in Obesity


Appears that leptin is primarily a signal
that is active in response to insufficient
energy supply rather than one that is
activated to prevent an oversupply of
energy
Apparent ineffectiveness of leptin in obese
persons despite high circulating levels
raises questions of whether "leptin
resistance" is operating in these individuals
& whether it can be overcome to benefit
overweight patients
Latest Research Finding about
Leptin
Researchers have successfully used
hormone leptin to treat patients suffering
from lipodystrophy-rare & difficult-to-treat
disorder that shares some characteristics
of typical type 2 diabetes
 People with lipodystrophy have few or no
fat cells & thus lack leptin, a hormone
produced by & stored in fat cells

Latest Research Finding about
Leptin – What is lipodystrophy?


Because they have no fat cells, people with
condition usually store huge amounts of lipids
(fat) in inappropriate places like muscle or liver
& have extremely high levels of lipids in their
blood
They are likely to be insulin resistant-meaning
their bodies don't readily respond to insulinhormone that allows muscle & fat cells to
properly use glucose.
Another Latest Research Finding
Establishes a new connection in
metabolic machinery, tying leptin to
crucial pathway in fat metabolism in
muscle
 Pathway suggests a role for leptin in
clearing fat out of cells and sheds light on
connection between diabetes & obesity.

Another Latest Research Finding
In light of new knowledge about leptin's
role in fuel metabolism, it makes sense to
revisit idea of targeting leptin's actions to
treat obesity
 Obese people develop resistance to
leptin, so ability to target downstream
pathway & bypass leptin resistance may
be more beneficial than treating with
leptin itself
