[acb-diabetics] obesity as protection against diabesity

[Patricia LaFrance-Wolf]

This article originally posted 

15 March, 2010

 and appeared in  

Issue 513

Obesity as Protection against Metabolic Syndrome, Not Its Cause

The collection of symptoms that is the metabolic syndrome -- insulin
resistance, high cholesterol, fatty liver, and a greater risk for diabetes,
heart disease,

and stroke -- are all related to obesity, but, according to a new review in
the March 9th issue of the 

Cell Press

 publication "Trends in Endocrinology and Metabolism," not in the way you
probably think they are. 

Advertisement 

Roger Unger of the University of Texas Southwestern at Dallas, tells us
that, obesity is the body's way of storing lipids where they belong, in fat
tissue,

in an effort to protect our other organs from lipids' toxic effects. It's
when the surplus of calories coming in gets to be too much for our fat
tissue

to handle that those lipids wind up in other places they shouldn't be, and
the cascade of symptoms known as metabolic syndrome sets in. 

It comes down to simple facts that all of us know on some level or another:
Americans since the 1950's have been eating too much high-calorie food
loaded

with carbs and fat (what Unger calls "potent adipogenic nutrient mixtures")
and, thanks to modern technology, we move far too little. Until that
changes,

Unger doesn't see any end to the growing epidemic of metabolic syndrome.
Still, our metabolisms aren't broken; the pathways that squirrel fat away as
an

energy source for use in lean times are just completely overwhelmed. "We are
pushing our homeostatic capability to the maximum," says Unger, who coined

the term "lipotoxicity" in 1994. "Overnutrition used to be rare -- reserved
for those in the castle. Today, it's just the opposite. Bad calories are so

cheap that anyone can afford to get overweight." 

Unger cites plenty of evidence in support of a protective role for obesity.
Genetic manipulations in mice that increase or decrease fat formation have
provided

evidence that adipogenesis, meaning the generation of fat cells, delays
other metabolic consequences of overeating. The reverse is also true, he
writes.

Obesity-resistant mice have in some cases been found to develop severe
diabetes upon eating too much, as a result of lipid accumulation in tissues
other

than fat. 

There is some disagreement in the field about whether insulin resistance is
a primary cause of metabolic syndrome or just one of its features, Unger
notes.

But on this, too, he has a clear view. Insulin resistance is not the cause
of metabolic syndrome, he says, it is a "passive byproduct" of fat
deposition

in the liver and muscle once storage in fat cells begins to fail. 

It also makes sense in Unger's estimation that cells that have already taken
on too much fat would begin to exclude glucose, causing its levels in blood

and urine to rise. Once in cells, glucose becomes a substrate for the
production of more fat. "The body is doing what we should have done - keep
excess

calories out - and it may be protective," Unger says. 

At the center of the transition from protective obesity to metabolic
syndrome is resistance to the fat hormone leptin, well known for its
appetite-suppressing

effects, Unger says. The hormone is also responsible for partitioning fat in
the body. The rise of leptin as fat stores grow is therefore an adaptive
response,

but that can only go so far before resistance sets in. 

Based on the genes they carry, some people will be better able to sustain
lipid storage in fat and can get away with being overweight, even obese,
without

the other symptoms. Eventually, though, the need to cut calories is
something all of us will face. 

"Once you reach a certain age, almost everybody is leptin resistant," he
says. "Nature stops protecting you once you pass the reproductive years,"
requiring

all of us to watch our diets and do exercise. 

Unger's perspective comes from the research he does at UT Southwestern's
Touchstone Center for Diabetes Research and a thorough understanding of the
scientific

literature, but it also stems from his own memories in childhood when one
only saw fat ladies at the circus. "That's how unusual it was," he says.
"The

younger you are, the more skewed your perception is of an epidemic that
surrounds you." 

Unger concludes his review article this way: "Based on evidence reviewed
here, it seems that prevalent forms of metabolic syndrome and T2DM [Type 2
diabetes

mellitus] result from unremitting caloric surplus complicated by failure of
adipocytes to maintain protection against lipotoxicity. If one imagines the

USA population to be unwitting volunteers in the largest (300 million
subjects) and longest (50 years) clinical research project in history, the
specific

aim of which was to determine if the deleterious effects of sustained
caloric surplus in rodents also can occur in humans, the outcome of the
project becomes

clear -- after 50 years of exposure to an inexpensive calorie-dense diet
high in fat and carbohydrates, 200 million subjects are overweight and >50
million

have metabolic syndrome. The failure of healthcare providers and
pharmaceutical industries to contain the pandemic suggests that elimination
of 'bargain

basement' calories will be required to 'price obesity out of the market.'
Unfortunately, this would have profound socioeconomic implications: How do
we

tax excessive calories while at the same time guaranteeing sufficient access
to high-quality foods for the underprivileged?" 

Scherer et al.: "Gluttony, sloth and the metabolic syndrome: a roadmap to
lipotoxicity."  

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