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The fifth meeting of the Oxford Health Alliance in Sydney,
Australia, on Feb. 25 to 27 dealt with obesity.
Obesity, according to one of the American
delegates, Lawrence Gostin, a professor at Georgetown and Johns
Hopkins universities, will kill in the next 10 years more people
than global terrorism and yet “there’s a political paralysis in
dealing with the issue.”
“[T]he human costs,” he continued “are
frightening when we consider that obesity could shorten the average
lifespan of an entire generation resulting in the first reversal in
life expectancy since data collecting began in 1900.”
The World Health Organization (WHO) estimates
that one in 10 adults in both rich and poor countries are obese. In
some rich countries like the US as much as 25 percent of the
population is obese.
The Sydney Resolution recommended four courses
of action. First, make towns and cities healthier places to live in.
Second, physical activity must become a daily part of a person’s
routine. Third, eat less fat and salt; make fresh foods affordable.
Fourth, stop smoking and cut down carbon emissions.
Nothing wrong with any of these except that they
are all preventative. The treatment of the obese should be the other
part of the equation.
However, this may not be easy because “getting
at the causes of obesity and related metabolic disorders is a
formidable challenge, in part because so many body systems are
affected.” (Brent E. Wisse, Francis Kim, Michael W. Schwartz,
“An Integrative View of Obesity,” Science, Nov. 9, 2007).
For this reason, cause and effect are difficult
to establish. But Wisse et al think that getting down to the level
of the cell might offer solutions.
The response of cells of many types is the same
whenever they are exposed to more nutrients than the body needs to
maintain its energy balance. “In this light,” the three doctors
from the Department of Medicine of Harborview Medical Center and the
University of Washington at Seattle said that, “the successful
identification of shared cellular response that underlie disease
requires a broad and integrative approach that may ultimately reveal
more effective obesity treatment strategies.”
Key to understanding obesity is the process
called energy homeostasis or dynamic equilibrium. This process
begins in those parts of the brain that regulate appetite and energy
metabolism; signals circulate throughout the body to keep track of
the status of body fuel stores such as glucose and free fatty acids
as well as hormones like insulin and leptin. When these signals
detect a decrease due to weight loss, specialized neurons in the
hypothalamus trigger the urge to eat in order to restore depleted
body fuel stores.
But when information that more nutrients than
can be metabolized by the cells is fed back to the brain, the
circulating signals increase to protect the body against changes in
nutrient stores.
Thus, obesity is not a passive accumulation of
body fat but an active defense of an elevated level of body fat.
This is key to the understanding of obesity.
When nutrients exceed energy expenditure, the
responses in many cell types, including the immune cells result in
metabolic dysfunctions. Among these are oxidative stress or the
production of reactive oxygen in the mitochondria and the disruption
of the functioning of the endoplasmic reticulum, a network of
membrane in the cytoplasm of the cell that are involved in protein
and lipid synthesis. Both reactions cause inflammation, preventing
the mitochondria from processing the nutrients.
Inflammation appears to be a common reaction whether
they are the cells of the blood vessels, the liver, the muscles, the
fat tissues, and the immune cells. Inflammation also blocks the
action of insulin, the hormone that helps the cells metabolize
nutrients.
If nutrient excess persists, insulin resistance
increases and inflammation worsens. The brain loses its ability to
detect the increases in body fuel stores as “it actively defends
what it perceives to be a stable, unchanging amount of body fat.”
This could be the link between obesity and Type
II diabetes. It’s possible that the same dysfunctions affect the
cells in the pancreas that secrete insulin. Insulin resistance
results in the inability of those cells in the pancreas to meet the
increased demand for insulin.
Nutrient excess has also a “deleterious”
effect on vascular tissues. A major function of the endothelial
cells that line blood vessels is to produce nitric oxide, a compound
that dilates blood vessels so that they are wide enough for blood to
circulate. This could be the link between nutrient excess and heart
disease.
All this shows that obesity is a whole body
disease. It affects most, if not all, body systems. The
interrelationships are still not well understood.
It’s for these reason that Wisse and his
collaborators suggest “more integrative approaches for studying
metabolic disease [that] may ultimately inform strategies aimed at
preventing or reversing obesity and its sequelae.”
In the meantime, the preventative approach
suggested by the Sydney Resolution is all we can do at this time.
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