Enzyme flips body’s ‘fat switch’

U. WARWICK (UK) — Discovery of a mechanism that controls the body’s “fat switch” may help explain why some people have a swift metabolism and others are in a constant struggle to control their appetite.

The enzyme, Carnitine palmitoyltransferase 1A (CPT1), has a switch which is thrown depending on the composition and curvature of its cellular membrane. This is the first time such a mechanism has been described and may possibly be unique, reflecting the importance of the protein to cellular function.

Its activity determines whether individuals will suffer from fatty liver in one extreme or ketosis in the other. The finding is expected to advance understanding of how proteins regulate appetite control and insulin secretion.

Reported in the Journal of Biological Chemistry, the research, led by Victor Zammit, professor of metabolic and vascular health at the University of Warwick, discovered that CPT1 is the key protein that regulates fatty acid oxidation in the liver and is critical for metabolism.

“Knowing that the CPT1 enzyme can switch and what controls it will ultimately lead to a better understanding of why some people appear to have a speedy metabolism and others struggle to curb their appetite.

“We are making great inroads to understanding the science behind our metabolism and how at cellular level it changes according to the influence of different factors—be they nutritional or hormonal,” he says.

The work is important for clinical practice because having discovered the molecular mechanism, it should now be possible to design drugs that flick the switch of CPT1 in one way or the other, depending on the requirements of individual patients and the tissue that needs to be affected.

For example, drugs can be developed for patients suffering from diabetic keto acidosis, a condition when insufficient insulin caused the body to start breaking down fat, so that the enzyme is inhibited to oxidize fewer fatty acids, Zammit says.

“This would be a major breakthrough in tackling the obesity crisis we now face.”

Researchers from the University of Southern California, Los Angeles, contributed to the study.

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