Published: Sep 14, 2013 | Updated: Sep 16, 2013
By Elizabeth DeVita Raeburn, Contributing Writer, MedPage Today

Full Story:  http://www.medpagetoday.com/Endocrinology/MetabolicSyndrome/41553

Action Points

• The production of fructose from glucose in the liver contributes to the development of metabolic syndrome in mice.
• Note that the animal findings might provide context for studies suggesting that sugary drinks are a culprit in the epidemic of obesity in humans.

The production of fructose from glucose in the liver contributes to the development of metabolic syndrome in mice, says a study published online September 10 in Nature Communications.

The study compared wild type mice and two types of knockout mice incapable of converting glucose into fructose or degrading fructose in the liver. After 14 weeks of a diet of 10% glucose and regular food, the normal mice exhibited signs of metabolic syndrome — an increase in energy intake and body weight, visceral obesity, fatty liver, elevated insulin and hyperleptinemia. The knockout mice that couldn’t process fructose did not.

The changes in the wild type mice were brought on by fructose converted from glucose via the polyol pathway, wrote Miguel A. Lanaspa, DVM, PhD, asssistant research professor of medicine at the University of Colorado, and his co-authors.

The polyol pathway is triggered by high serum glucose. When that happens, aldose reductase (AR) metabolizes glucose to sorbitol, which is converted to fructose by sorbitol dehydrogenase.

“Consistent with this hypothesis, we found elevated levels of fructose and sorbitol in the liver of [wild type] mice given glucose water compared with mice given regular water,” the authors wrote. “Serum fructose levels were also higher in glucose-fed [wild type] mice compared with [wild type] controls.”

What’s more, the increase in levels of fructose and sorbitol in the liver of the wild type mice was accompanied by higher expression of aldose reductase and the enzyme the knockout mice lacked, ketohexokinase (KHK).

The study “provides new insights into how carbohydrates may cause obesity, fatty liver and insulin resistance,” the authors wrote. “We are now suffering a huge epidemic of metabolic syndrome… and we can correlate the onset of the epidemic with the increased consumption of sugars,” said Lanapa.

But while many articles have linked sugar consumption, primarily as high fructose corn syrup, to the development of metabolic syndrome, there’s still controversy, said Lanaspa. The fact that low carbohydrate diets, like the Atkins diet, are partially successful suggests that dietary carbohydrates are at least partially responsible for metabolic syndrome, said Lanapas.

But there’s been disagreement, he says, about whether glucose or fructose is to blame.

“Here,” said Lanaspa, “we show two things — glucose causes metabolic syndrome as denoted by fatty liver and insulin resistance in mice, and that the mechanism is mediated by the conversion of glucose into fructose and its metabolism in the liver.”

It confirms, he said, that while glucose and foods with a high glycemic index can cause metabolic syndrome, fructose — which has a low glycemic index — is a problem as well.

Whether this phenomenon is also occurring in humans remains to be determined, the authors wrote.

The animal findings, however, might provide context for studies suggesting that sugary drinks are a culprit in the epidemic of obesity in humans.

High-fructose corn syrup contains glucose. Soft drinks containing high-fructose corn syrup deliver high-glucose solutions (4-6%) to the gut. And sucrose-containing soft drinks deliver a similar dose, after the sucrose is broken down into fructose and glucose. These drinks are a “special problem,” said the authors, since the glucose enhances fructose absorption.

Consistent with this, they wrote, are studies of overweight humans who consume an excess of soft drinks. In one study of overweight subjects they cited, the consumption of a liter a day of a sugary soft drink for six months was associated with “significantly more” visceral fat, hepatic fat, and serum triglycerides compared with a group given diet soda, milk or water.