“Like adding extra fat to a diet”: Study reveals fructose inhibits liver’s fat-metabolizing ability

02 Oct 2019 --- High levels of fructose in the diet inhibit the liver’s ability to metabolize fat properly. This is according to researchers at Joslin Diabetes Center in Boston, US, who also found that equally high levels of glucose in the diet actually improve the fat-burning function of the liver. This explains why high dietary fructose has more negative health impacts than glucose does, even though they have the same caloric content. The researchers now believe that a drug blocking fructose metabolism could prevent the negative actions of fructose. These actions include fatty liver disease and adverse metabolic consequences, such as impaired glucose tolerance and Type 1 diabetes.

“The most important takeaway of this study is that high fructose in the diet is bad,” says C. Ronald Kahn, Chief Academic Officer at Joslin and the Mary K. Iacocca Professor of Medicine at Harvard Medical School and lead author on the study published in Cell Metabolism.

“Fructose is not bad because it has more calories, but because it has effects on liver metabolism to make it worse at burning fat. As a result, adding fructose to the diet makes the liver store more fat, and this is bad for the liver and bad for whole body metabolism. Surprisingly, when you switch the sugar in the diet from fructose to glucose, even though they’re both equally caloric, the glucose doesn’t have that effect. In fact, if anything, overall metabolism is somewhat better than if they just were on a plain high-fat diet.”

He adds that as fructose makes the liver accumulate fat, it acts almost like adding more fat to the diet. This contrasts the effect of adding more glucose to the diet, which promotes the liver’s ability to burn fat, and therefore actually makes for a healthier metabolism.

C. Ronald Kahn, Chief Academic Officer at Joslin and the Mary K. Iacocca Professor of Medicine at Harvard Medical School and lead author on the study.A series of studies
The researchers have conducted multiple studies concerning what role high fructose in the diet plays in terms of insulin resistance and metabolic syndrome. In this paper, they sought to pinpoint the mechanism behind fructose’s negative effects. 

During various animal studies, the team compared the effects on the metabolism of six different diets: regular chow, chow with high fructose, chow with high glucose, a high-fat diet, a high-fat diet with high fructose, and a high-fat diet with high glucose. They also analyzed different known markers of fatty liver to determine the effects of each diet.

One aspect of this was analyzing the levels of acylcarnitines – which are produced when the liver burns fat – in the liver’s cells. High levels of acylcarnitines are a negative sign as it means there is lots of fat in the liver. The levels were highest in the animals on the high-fat plus high fructose diet. They were lower in the high-fat plus glucose diet than in the plain high-fat diet, which reflected previous observational findings and indicated that glucose performed an assistive fat-burning action in these animals.

The researchers then monitored the activity of CPT1a, a critical enzyme for fat-burning. In this case, the higher levels of CPT1a, the better, as they indicate that mitochondria are performing their fat-burning jobs correctly. However, in the high-fat plus fructose diet, the researchers found that levels of CPT1a are low and their activity was very low, meaning mitochondria cannot function properly.

“When mitochondria are healthy, they have this nice ovoid shape and crosshatching,” says Dr. Kahn. “In the high-fat plus fructose group, these mitochondria are fragmented, and they’re not able to burn fat as well as the healthy mitochondria. But looking at the high-fat diet plus glucose group, those mitochondria become more normal-looking because they are burning fat normally.”

These findings combined prove that both high-fat and high-fat plus fructose diets damage mitochondria and make it easier for the liver to synthesize and store fat rather than burn it.

Another study earlier this year found that consuming a modest amount of high-fructose corn syrup – the equivalent of a can of soda for humans – every day promotes the growth of intestinal tumors in mice models of the disease.

Edited by Katherine Durrell