Behind the Headlines

Thursday July 16 2009

Naringenin boosts the metabolism of fatty acids in mice livers

“Grapefruit ingredient could be used for diet pill,” reported The Daily Telegraph. The newspaper said that naringenin, the chemical compound that gives grapefruit its bitter taste, could be used to create a diet pill. The news is based on a study in mice, which found that the chemical made their livers burn fat instead of storing it after a meal. The researchers are said to believe that it has the potential to help obesity sufferers and possibly fight diabetes, as the process also helps to balance insulin and glucose levels.

As mentioned by the newspaper, this was a study in mice, therefore it has limited applicability to humans. In addition, the dose given to the mice was quite high, and the researchers confirm that a human equivalent would be far higher than could be obtained just by eating grapefruit. A drug that is based on the compound might be possible, but it would need to be shown to be effective and safe for humans first, and would probably take several years to develop.

Where did the story come from?

This research was carried out by Erin E. Mulvihill and colleagues from the Robarts Research Institute in Ontario, Canada. The study was supported by grants from the Heart and Stroke Foundation of Ontario and various fellowships. The study was published in Diabetes, the peer-reviewed medical journal of the American Diabetes Association.

What kind of scientific study was this?

In this animal study, the researchers were seeking to confirm in live mice an effect that they had observed in the laboratory. This previous laboratory research had indicated that naringenin, a type of flavonoid, could lower some types of lipids (fats) in the blood. The researchers say it appeared to do this by stopping the very low-density lipoproteins (VLDLs) stored in the liver from being secreted by the liver cells. This is similar to the action of the hormone insulin, to which people with abdominal obesity (sometimes referred to as metabolic syndrome) may become resistant.

Metabolic syndrome is a diagnosis made in people who have several risk factors for heart disease, including abdominal obesity, high triglyceride fats in the blood, high blood pressure and impaired metabolism of glucose.

Naringenin is a type of flavonoid, a chemical metabolised by plants that is thought to have antioxidant properties. In this case, the researchers were not interested in testing the antioxidant properties, but concentrated on the effect of the chemical on liver cells (hepatocytes).

The researchers first bred mice that were deficient in the receptors for low-density lipoproteins, a type of circulating protein that carries cholesterol. When these mice are fed a high-fat diet (42% calories from fat) they become obese, similar to the way in which metabolic syndrome develops in humans. When the mice were eight to 12 weeks old, they were separated into four groups for comparison. One group was fed a normal mouse diet, a second group was fed the high-fat diet, and two further groups were fed the high-fat diet with either 1% or 3% concentrations of naringenin added. They repeated these experiments in normal (wild-type) mice, which were fed the high-fat diet for 30 weeks.

After four weeks of feeding freely on their allocated diets, the mice were tested for VLDL production, insulin and glucose.

What were the results of the study?

The mice fed a high-fat diet with added naringenin had better lipid metabolism, but their energy intake and fat absorption were unaffected compared to the normal-diet and high-fat diet mice.

Naringenin increased the metabolism of fatty acids in the liver, and prevented the production of lipids in the liver and muscle by reducing insulin levels. It also decreased the ability of liver cells to make cholesterol.

The high-fat diet increased hepatic (liver) lipids and led to increases in glucose and insulin levels. The researchers say this resulted from impaired glucose tolerance and reduced sensitivity to the effects of insulin. The naringenin, at 3% concentration, added to a high-fat diet given to normal mice had similar effects on insulin and glucose metabolism.

What interpretations did the researchers draw from these results?

The researchers conclude that by correcting many of the metabolic disturbances linked to insulin resistance, naringenin, has the potential for treating metabolic syndrome in humans.

What does the NHS Knowledge Service make of this study?

This study in mice has further established how naringenin might act on complex lipid and glucose metabolic pathways and provides further avenues for drug discovery and development. There are some points to note about the study:

  • It is not clear how the dose of naringenin given to the mice relates to a potential human dose, or to the average amount found in a grapefruit. One of the researchers has said that the concentrations of the citrus-derived flavonoid being studied are at higher levels than one would obtain through a normal diet.
  • The compound was being tested for its preventative properties, to prevent weight gain and influence the metabolic processes of mice before they became obese. Its effectiveness at promoting weight loss in obese mice will need further investigation.

The bottom line is that this study does not mean that eating grapefruits will cause weight loss.

Edited by NHS Choices

Links to the headlines

Grapefruit ingredient could be used for diet pill. The Daily Telegraph, July 16 2009

Grapefruit offers a bitter route to beating obesity as 'it makes liver burn fat instead of storing it'. Daily Mail, July 16 2009

How an ingredient in grapefruit could help us lose weight. Daily Express, July 16 2009

Links to the science

Mulvihill EE, Allister EM, Sutherland BG, et alNaringenin prevents dyslipidemia, apoB overproduction and hyperinsulinemia in LDL-receptor null mice with diet-induced insulin resistance. Diabetes 2009; published online before print July 10 

Further reading

Brunner E, Rees K, Ward K, Burke M, Thorogood M. Dietary advice for reducing cardiovascular risk. Cochrane Database of Systematic Reviews 2007, Issue 4

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