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Fructose metabolism in the brain may increase food intake, obesity: Review

By Stephen Daniells , 30-Mar-2009
Last updated on 30-Mar-2009 at 11:38 GMT

The way fructose is metabolised in the brain may increase food intake and lead to obesity, according to a new review from the US.

“We feel that these findings may have particular relevance to the massive increase in the use of high fructose sweeteners (both high fructose corn syrup and table sugar) in virtually all sweetened foods, most notably soft drinks,” said lead researcher M. Daniel Lane from The Johns Hopkins University School of Medicine.

Dr Lane told FoodNavigator that he did not wish to give the impression that HFCS is the only problem, “since sucrose/table sugar contains only a slightly lower percentage of fructose than HFCS”.

Dr Lane added consumption of both HFCS and table sugar in the USA is about 65.8 kg (145 pounds) per year.

“I hasten to point out that the situation is probably most critical with the younger population, particularly in the USA, where many children receive enormous amounts of fructose in soft drinks which they consume continuously and acutely. This would be expected to lead to substantial blood levels of fructose, as well as glucose,” he told this website.

Findings

Writing in the journal Biochemical and Biophysical Research Communications, Dr Lane and Seung Hun Cha report that recent studies (largely in their laboratory) have shown that glucose and fructose act quite differently in the brain.

Two papers published in PNAS in 2007 and 2008 showed that glucose and fructose signal in the brain through the malonyl-CoA signaling pathway and have inverse effects on food intake.

Dr Lane told FoodNavigator that fructose is metabolized more rapidly that glucose, and therefore exerts its effects before glucose.

“As a consequence of this more rapid rate of fructose metabolism ATP [adenosine triphosphate] is depleted and thereby causes the level of AMP [adenosine monophosphate] to rise, which in turn initiates the signaling pathway that leads to an increase in appetite/ food intake,” he explained.

Science

The scientists supplied fructose to animals using intraperitoneal (ip) injection (injection into the abdomen) and intracerebroventricular (icv) injection (injection into the brain’s blood system).

Dr Lane and his co-workers found that fructose was metabolised more rapidly than glucose in the brain.

In [the hypothalamus and the liver] the rate of glucose is slowed by the early regulated steps in the glycolytic pathway, most notably by [the enzyme] phosphofructokinase (PFK), the rate-limiting step in glucose metabolism,” explained Dr Lane.

“Fructose on the other hand, enters the glycolytic pathway at a point downstream of PFK. Therefore, fructose by-passes this rate- limiting step, thus even in the presence of glucose, fructose is metabolised more rapidly than glucose,” he added.

In the most recent PNAS article (2008, Vol. 105, No. 44, pp. 16871-16875) the researchers noted that the effect of fructose on the food intake is dependent on the ability of fructose to cross the blood- brain barrier or enter the brain through circumventricular structures with weak blood-brain barriers, notably in the arcuate nucleus”.

Reaction

Commenting on the findings of the study, Dr James Rippe from the Rippe Lifestyle Institute (RLI) told FoodNavigator: “While this may be interesting science, it must be approached with extreme caution when attempting to extrapolate this type of information to human nutrition, behavior or health.”

“To speculate, as Lane and Cha do, that the biochemical pathways they describe can lead to over consumption of food and obesity is highly speculative and probably incorrect,” added Dr Rippe.

To read a fuller account of Dr Rippe’s response, please click here .

Source: Biochemical and Biophysical Research Communications Published online ahead of print, http://dx.doi.org/10.1016/j.bbrc.2009.02.145 |“Effect of glucose and fructose on food intake via malonyl-CoA signaling in the brain” Authors: M.D. Lane, S.H. Cha

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