Lee Swanson Research Update

Insufficient ALA Could Be Linked to Obesity Trend

September 2010

A new study suggests that a deficiency in alpha-linolenic acid (omega-3) coupled with a chronic excess of linoleic acid (omega-6) could lead to "inherited obesity."

The study, published in the Journal of Lipid Research, describes an increase in fat mass of mice over several generations when fed an "unbalanced western diet."

In addition to trans-generational weight gain, the research also observed the onset of metabolic disorders such as insulin resistance and the expression of the inflammatory genes involved in obesity as generations advanced.

"Collectively, our data show that continuous exposure to a high-fat diet combined with a high LA:LNA (omega-6:omega-3) ratio over generations triggers a discrete and steady increase in inflammatory stimuli, accompanied by enhancement of fat mass," the researchers wrote.

The beneficial role that polyunsaturated fatty acids can have on health is well established. However, when their intake is unbalanced, these essential fatty acids can enhance factors that can induce obesity and may have serious long-term effects on human health.

During the last 40 years western societies have seen increases in the level of calories ingested, alongside an increase of over 250% in levels of omega-6 intake and a fall in levels of omega-3 of 40%. This change in diet has coincided with a steady rise in obesity levels through the generations.

Over this time the ratio of omega-6 to omega-3 in a typical western diet has shifted from the recommended 5-to-1 to 15-to-1 in much of Europe, and can be as high as 40-to-1 in the United States.

Alpha-linolenic acid (ALA) omega-3 is an essential fatty acid that the body cannot make and therefore must be consumed in the diet. Good sources of ALA include: flaxseed, soybeans, walnuts and olive oil. The U.S. Institutes of Medicine recommends an ALA intake of 1.6 grams per day for men and 1.1 grams per day for women.

The new research, led by Gerard Ailhaud at the Universite de Nice Sophia-Antipolis in France, exposed several generations of mice to a high omega-6 and low omega-3 western diet and assessed the consequences.

The mice were given unrestricted access to food and water (ad libitum conditions) over several generations in order to allow the mice to self-regulate the intake according to biological needs.

"We chose purposely ad libitum conditions to expose both male and female mice across several generations to a western-like diet," the researchers explained.

The results of the study observe that under conditions of genetic stability and with no change to routine, four generations of a western-like fat diet were sufficient to gradually increase fat mass.

"A gradual trans-generational increase in adiposity can occur in mice fed a western-like diet," wrote the researchers.

The study suggests that an unbalanced diet can lead to changes in the expression of genes that control growth and immune factions.

A gene expression analysis of fat tissue over several generations of the mice observed "discrete and steady changes in certain important players, such as colony stimulating factor-3 (CSF-3) and Nocturnin."

The researchers said, "Our data show that expression of CSF-3 increased over generations in mice. These results strongly suggest a role for CSF-3 in stimulating growth of adipocyte progenitors."

The researchers conclude that in a genetically-stable animal population, exposure to a diet similar to that of westernized human populations was enough to cause the emergence of trans-generational obesity.

Ailhaud and his team suggest that the trans-generational "inheritance" of adipose tissue could be linked to the increased expression of the CSF-3 gene across generations that could enhance the proliferation of adipose progenitors—although further research into these links would be needed.

Journal of Lipid Research 51(8):2352-2361, 2010

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