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If you’re like most Americans, you are
struggling with at least a few extra pounds.
And if you’re over 40, those extra pounds are
probably accumulating with an unwelcome
preference for your mid-section.
Spare-tire fat distribution is more than an
unsightly annoyance. Fat that accumulates in
your belly is extremely dangerous! That’s
because it promotes the release of
proinflammatory “cytokines” that
seem to be involved in just about every
age-related degenerative disease.
Abdominal obesity is a hallmark
characteristic of metabolic syndrome, also
known as “syndrome X,” or “pre-diabetes.”
Metabolic syndrome is a
constellation of insidious pathological
processes that place you at significantly
increased risk for heart disease, diabetes,
cancer, stroke, and dementia.
Until very recently, there appeared little
most people could do to significantly reduce
excess abdominal fat. Fortunately, cutting-edge
research has identified a potential
reversible mechanism of both
stubborn middle-aged weight gain and associated
markers of metabolic syndrome such as high
blood levels of glucose, LDL, and C-reactive
protein.
What is Leptin?
Leptin is a hormone, produced
by adipocytes (fat cells), that functions to
maintain a lean body composition by at least
two distinct mechanisms:
First, it modulates appetite by binding to a
specific area of the brain, known as the
hypothalamus, where it signals
satiety.1 Normally, a
well-nourished state is reflected by an
increase in leptin production and, in turn, the
elevated serum leptin signals the hypo-thalamus
to limit hunger. And second, leptin enhances
the body’s ability to access and utilize fat
stores as an energy source.2
Leptin caught the attention of the medical
community in the mid-90s when its
administration to genetically obese mice caused
the animals to rapidly shed 30% of their body
weight in two weeks with daily leptin
injection.3 In 1995,
scientists believed they had finally uncovered
the holy grail of weight control. Human studies
were quickly underway, but when obese
individuals received leptin injections, the
expected results never appeared: appetites were
not suppressed, and weight was not lost.
Although investigators were disappointed
when supplemental leptin failed to induce
weight loss in humans, they were not entirely
surprised. Previous research had revealed that
overweight individuals already had far more
serum leptin than their normal-weight
counterparts. In fact, studies have
conclusively demonstrated that both the total
amount of body fat—as well as the size of the
individual fat cells—that an individual
possesses, correlate directly to the amount of
leptin he or she produces.3,4 In short,
the fatter you are, the more leptin you will
have floating in your bloodstream.
Which begs the obvious question: how can a
compound that normally functions to maintain
leanness be consistently most elevated in
individuals who are most obese?
Researchers believed that the apparent
paradox could be explained by an acquired
resistance to
leptin.4,5 Since
being overweight leads to chronically
elevated levels of the hormone, they
hypothesized that prolonged exposure to
this leptin overload could eventually
cause target tissues to become “immune”
to the effects of leptin, losing the
normal capacity to respond to
it.5 More
than a decade later, investigators are
still hard at work elucidating what has
turned out to be an exceedingly
complicated interplay between genes and
hormones. Nevertheless, many aspects of
leptin resistance have already been
successfully deciphered and described in
the scientific literature.
For example, we now know that leptin
resistance shares a lot in common
with insulin resistance. Like insulin
resistance, leptin resistance is a
chronic inflammatory condition that contributes
directly to progressive weight gain, stubborn
weight loss, and subsequent weight regain. But
the cosmetic consequences of leptin resistance
are the least of your worries! Behind the spare
tire lies a quagmire of physiological
dysfunction that places you at enormously
increased risk for conditions ranging from
diabetes, heart disease, and cancer, to
stroke6 and
dementia.7
How Leptin Resistance Helps Keep You Fat
and Makes You Sick
Being chronically overweight leads to
chronically elevated leptin levels, and
chronically elevated leptin eventually causes
target tissues—most notably adipocytes and
neurons—to lose the capacity to respond to
it.
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As the size and number of your adipocytes
increase with weight gain, they pump more and
more leptin into the circulation
in an attempt to send the message to the brain
that fat stores are adequate, and appetite
needs to be reined in. However, because these
same fat cells are constantly bathed in
elevated levels of leptin, they progressively
lose sensitivity for the very leptin they are
working overtime to produce in excess. As you
might imagine, inadequate receptor sensitivity
translates to diminished responsiveness, which
has two unfortunate results: first, normal
fatty acid oxidation (fat burning) within the
adipocyte significantly declines and, second,
the adipocyte becomes less inclined to absorb
free fatty acids from the circulation. The
resulting excess of fatty acids floating in the
bloodstream causes a functional insulin
resistance in peripheral tissues like
muscle.8
As with leptin-resistant fat cells,
insulin-resistant muscle cells lose their
responsiveness—in this case to insulin. As a
result, glucose molecules are blocked from
entering muscle tissue, causing blood sugar to
rise. The liver senses hyperglycemia and, in an
effort to prevent progression to full-blown
type 2 diabetes, liver cells respond by
breaking down the rogue sugar molecules and
transforming them into more free fatty acids.
In turn, the additional free fatty acids
contribute to increased fat stores, increased
leptin production, escalating leptin
resistance, and the vicious cycle continues to
snowball.9
Unfortunately, adipocytes are not the only
cells that submit to the effects of chronically
elevated leptin. Once leptin
resistance begins to take hold,
neurons in the hypothalamus also show decreased
responsiveness to circulating leptin. However,
these same neurons respond normally to leptin
if it is injected directly into the brain,
suggesting that, unlike adipocytes, neurons
retain their leptin receptors despite leptin
resistance.10,11 Thanks
to a group of scientists from the University of
Pittsburgh’s Department of Cell Biology and
Physiology, we are now one step closer to
understanding the mechanisms underlying this
phenomenon.12
The Pittsburgh group recently identified a
class of proteins in human blood that interact
directly with serum leptin. One of these is
C-reactive
protein (CRP),12 a marker
of systemic inflammation and predictor of
cardiac risk that’s back in the spotlight
thanks to a recent study showing that elevated
CRP levels double a patient’s chances of dying
within the first 28 days following acute
myocardial infarction.13 Previous
research has linked elevated CRP, produced by
adipocytes and liver cells, to both increased
adiposity and increased plasma leptin. But the
real breakthrough came when investigators
discovered that human CRP binds leptin and, in
doing so, may prevent leptin from signaling
satiety.
In pre-clinical studies, infusion of human
CRP into obese, leptin-deficient mice blocked
the normally observed effects of leptin
supplementation and prevented weight loss. In
mice genetically engineered to produce human
CRP, leptin’s effects on appetite control and
weight regulation were completely blunted. The
authors suggest that human CRP binding to
leptin may interfere with leptin’s ability to
pass through the blood-brain barrier to reach
the hypothalamus.12
Without access to these appetite-controlling
neurons, it no longer matters how much leptin
is present in the bloodstream. Even in cases of
extreme obesity and correspondingly elevated
serum leptin, the satiety signal never gets
triggered because CRP binds leptin and prevents
it from crossing the blood-brain barrier to
suppress appetite. By blocking leptin’s
physiological functions, CRP represents a
powerful component in the progression of
leptin resistance and escalating
weight gain.
What Can You Do About Leptin
Resistance?
You can do a lot to prevent systemic
inflammation and all its negative
consequences—including leptin
resistance—through lifestyle choices.
Avoiding proinflammatory high-glycemic
load and processed foods, supplementing with
anti-inflammatory omega-3 essential fatty
acids, and engaging in regular physical
activity are all well-established means by
which one can thwart the onset of chronic
inflammation and maintain a
healthy body weight. But what if you are one of
the millions of Americans who—due to a
combination of life circumstances, genetics,
and/or exposure to environmental
toxins14—have already
succumbed to some degree of chronic
inflammation and commensurate weight gain?
Unfortunately, no matter how faithfully you
embrace an anti-inflammatory lifestyle from
this day forward, research clearly indicates
that it will be more difficult for you to lose
weight if you are leptin-resistant.
15 And
if you’re overweight, you’re almost
certainly suffering from some degree of
leptin resistance. Plus, as
about 90% of people who have successfully
lost weight in the past will rapidly
attest, those pesky pounds have an
uncanny proclivity for reappearing—and
bringing some new friends along with them
when they do. Now, thanks to emerging
studies on leptin
resistance, researchers are
beginning to realize that weight
reduction itself may launch yet another
vicious cycle that makes it exceedingly
difficult to maintain leanness. Here’s
how it works:
As you may recall, leptin production
correlates to adiposity; it rises or falls
naturally with increasing or diminishing body
fat, respectively. However, if weight gain is
substantial or protracted enough to provoke the
development of leptin resistance, subsequent
weight loss appears to cause a state of
“relative leptin insufficiency.”
16 In
essence, after you’ve been overweight,
the amount of leptin your body requires
to stay lean may exceed what your “thin
self” (and correspondingly shrunken fat
stores) can produce. Once relative leptin
insufficiency rears its ugly head,
adaptations to muscle metabolism and
modulations in sympathetic and autonomic
hormones function make weight regain all
but inevitable.
Investigations endeavoring to override
relative leptin insufficiency with exogenous
leptin have had some early
success,17,18 but—even
if you don’t mind daily injections for
the rest of your life—leptin
supplementation is a slippery slope!
After all, it’s excess leptin that
instigates the vicious cycles of leptin
resistance in the first place. Moreover,
leptin does not exist in an isolated
vacuum of weight control. Like any good
hormone, leptin’s effects throughout the
body are far-reaching and complex; it may
be years before we have a satisfactory
grasp of the health repercussions of
casual leptin use. Already, current
research suggests that elevated leptin
provokes the growth of certain
malignancies, including many forms of
breast cancer (which helps explain the
higher breast cancer risk observed in
overweight women).19 Likewise,
chronically high serum leptin is believed
to increase stroke risk20 and
promote cardiac hypertrophy (enlargement
of the heart).21
From:
http://www.lef.org/magazine/mag2009/feb2009_Irvingia-Understanding-the-Risks-of-Leptin-Resistance_01.htm
Dr. Dingsor's comment: I
always tell my patients an anti-inflammatory
diet is not only good for pain but for reducing
your weight as well. Leptin resisitance
is a new concept, but you can battle the bulge
through doing the following:
- Start a lifestyle of being on an
anti-inflammatory
diet
- Supplement with Fish Oil (2 tsp
per day)
- Take a high quality
multi-vitamin
- Exercise daily
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Dr. Bryan Dingsor
is the owner of Watertown
Chiropractic P.C. in Watertown, SD. He
specializes in the treatment of many
musculoskeletal conditions and weight loss. For
an appointment, please call 605-882-2304
Today.
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