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Avocados are a nutritious food rich in unsaturated fats, fiber, and many bioactive plant compounds, including avocatin B, an enzyme that prevents fatty acids from being oxidized and becoming rancid. In people with obesity, free fatty acid concentrations in the blood are elevated (called lipotoxicity), a condition that impairs insulin sensitivity in skeletal muscle and contributes to the development of diabetes. Authors of a recent study detail their findings regarding the effects of avocatin B in carbohydrate and fat metabolism.

Diet-induced obesity causes insulin resistance, type 2 diabetes, and cardiovascular disease, in part due to lipotoxicity, although the exact mechanisms are unclear. Some investigators have suggested that the increased oxidation of fats in the mitochondria of skeletal muscle cells leads to these cells becoming insulin resistant; however, others have refuted this theory. In a previous study, this team of researchers discovered that avocatin B accumulates in mitochondria of leukemia cells, inhibiting fat oxidation, and inducing cell death.

The researchers conducted their study in three phases, including a trial in mice, a laboratory study of pancreatic cells, and a trial in humans. They fed mice a high-fat diet (60 percent of calories from lard) for eight weeks and then gave avocatin B to half of the mice and a placebo to the other half for five weeks. They measured glucose tolerance and insulin sensitivity. Next, the researchers exposed muscle cells and pancreatic beta cells, which produce insulin, to lipotoxicity and measured the ability of avocatin B to protect these cells. Finally, they conducted a randomized, double-blind, placebo-controlled trial in healthy human participants (average age, 28 years). The participants consumed either 50 milligrams or 200 milligrams of avocatin B per day or a placebo for 60 days in order to determine the safety of the drug.

The authors found that avocatin B reduced the amount of weight gained on a high fat diet and improved glucose tolerance and insulin sensitivity in mice. In both muscle cells and pancreatic beta cells, avocatin B inhibited fatty acid oxidation, increased glucose oxidation, and reduced the generation of reactive oxygen species, which are harmful to cells. Avocatin B-treated pancreatic beta cells produced more insulin, and muscle cells were more insulin sensitive. In humans, avocatin B was well-tolerated and was not associated with toxicity.

The authors concluded that avocatin B is an effective inhibitor of fatty acid oxidation, that its consumption at doses up to 200 milligrams per day is safe for humans, and that it may improve the metabolic dysfunction in those with diet-induced obesity.

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