| High-Fructose Corn Syrup
Causes Insulin Resistance
A new study in mice sheds light on the insulin
resistance that can come from diets loaded with high-fructose
corn syrup, a sweetener found in most sodas and many other processed
foods. The report in the March issue of Cell Metabolism
also suggests a way to prevent those ill effects.
The researchers showed that mice on a high-fructose diet were
protected from insulin resistance when a gene known as transcriptional
coactivator PPARg coactivator-1b (PGC-1b) was "knocked down"
in the animals' liver and fat tissue. PGC-1b coactivates a number
of transcription factors that control the activity of other genes,
including one responsible for building fat in the liver.
"There has been a remarkable increase in consumption of
high-fructose corn syrup," said Gerald Shulman of Yale University
School of Medicine. "Fructose is much more readily metabolized
to fat in the liver than glucose is and in the process can lead
to nonalcoholic fatty liver disease," he continued. NAFLD
in turn leads to hepatic insulin resistance and type II diabetes.
Metabolic syndrome and type 2 diabetes have both reached epidemic
proportions worldwide with the global adoption of the westernized
diet along with increased consumption of fructose, stemming from
the wide and increasing use of high-fructose corn syrup sweeteners,
the researchers noted.
High-fructose corn syrup, which is a mixture of the simple sugars
fructose and glucose, came into use in the 1970s and by 2005 the
average American was consuming about 60 pounds of it per year.
Overall, dietary intake of fructose, which is also a component
of table sugar, has increased by an estimated 20 to 40 percent
in the last thirty years.
Earlier studies had established that fructose is more readily
converted to fatty acids than glucose and had also linked high-fructose
diets to high blood levels of triglycerides (a condition known
as hypertriglyceridemia), NAFLD and insulin resistance. While
researchers had implicated a gene known as SREBP-1, a master regulator
of lipids' manufacture in the liver, much about the underlying
molecular connections between fructose and those metabolic disorders
remained mysterious.
In the new study, the researchers zeroed in on PGC-1b, a gene
known for boosting SREBP-1 levels. To test its role in the effects
of fructose, they blocked its activity in mice fed a diet high
in that sugar for four weeks.
Those treatments improved the animals' metabolic profiles by
lowering levels of SREBP-1 and other fat-building genes in their
livers. The mice also showed a reversal of their fructose-induced
insulin resistance and a threefold increase in glucose uptake
in their fat tissue.
"These data support an important role for PGC-1b in the
pathogenesis of fructose-induced insulin resistance and suggest
that PGC-1b inhibition may be a therapeutic target for treatment
of NAFLD, hypertriglyceridemia, and insulin resistance associated
with increased de novo lipogenesis," the researchers concluded.
The new study has "revealed the transcriptional coactivator
PGC-1b as a missing link between fructose intake and metabolic
disorders," wrote Carlos Hernandez and Jiandie Lin of the
University of Michigan Medical Center, Ann Arbor in an accompanying
commentary. "The findings …support the emerging role
of gene/environment interaction in modulating the metabolic phenotype
and disease pathogenesis. Thus, perturbations of the same regulatory
motif may produce vastly different metabolic responses, depending
on the specific combinations of dietary nutrients," they
continued.
Reference Source 128
March 6, 2009
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