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Fat may override body’s fullness signals: Study

By Stephen Daniells , 14-Sep-2009

Over-indulgence may be all fat’s fault, according to a new study which reports that fat molecules may over-ride the body’s appetite-suppressing signals.

Scientists from the University of Texas Southwestern Medical Center report that fat, and palmitic acid in particular, may signal the body’s cells to ignore the appetite-suppressing signals of leptin and insulin. Palmitic acid is a common saturated fatty acid occurring in foods such as butter, cheese, milk and beef.

Despite being a study with animals, lead researcher Dr Deborah Clegg said that the findings strengthen the common dietary recommendation that individuals limit their saturated fat intake.

It also strengthens calls for reformulation of food products to reduce saturated fat content. The UK’s Food Standards Agency, for example, launched the Saturated Fat and Energy Intake programme (SFEI) in February 2008, as part of a bid to tackle cardiovascular disease and obesity.

The tough draft recommendations call for certain biscuits, cakes and pasties to reduce their saturated fat levels by 10 per cent on 2008 levels by 2010, for example.

The findings of Clegg and her co-workers, published in the Journal of Clinical Investigation, support such calls.

“Normally, our body is primed to say when we’ve had enough, but that doesn't always happen when we're eating something good,” said Clegg. “What we’ve shown in this study is that someone's entire brain chemistry can change in a very short period of time.

“Our findings suggest that when you eat something high in fat, your brain gets 'hit' with the fatty acids, and you become resistant to insulin and leptin,” she added. “Since you're not being told by the brain to stop eating, you overeat.”

Over-riding the safety system

The researchers used rodents and showed that certain fats are able to activate a gene called PKCθ (Protein kinase C, theta), which can then override the signaling of leptin and insulin.

Using rodents, the Texas-based researchers exposed the animals to fat in different ways: By direct injection of palmitic acid, monounsaturated fatty acid and oleic acid (an unsaturated fatty acid) into the brain; infusion of the fats through the carotid artery, or feeding the animals through a stomach tube three times a day.

“We found that the palmitic acid specifically reduced the ability of leptin and insulin to activate their intracellular signaling cascades,” said Clegg. “The oleic fat did not do this. The action was very specific to palmitic acid, which is very high in foods that are rich in saturated fat.”

Furthermore, the effects appear to last for about three days, said Clegg, which may explain whey people say they are hungrier than normal on Mondays following a weekend of overindulgence.

The study represents the first report of PKCθ activation in the brain, said the researchers. The next step, said Clegg, is to determine how long it takes to reverse completely the effects of short-term exposure to high-fat food.

Source: The Journal of Clinical Investigation
Volume 119, Number 9, Pages 2577-2589, doi:10.1172/JCI36714.
“Palmitic acid mediates hypothalamic insulin resistance by altering PKC-θ subcellular localization in rodents”
Authors: A.-L. Lefevre, C. Cruciani-Guglielmacci, C. Magnan, F. Yu, K. Niswender, B.G. Irani, W.L. Holland, D.J. Clegg

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