Mitochondrial Gene Linked To Adult-Onset Obesity

Scientists in Australia have discovered that having just one copy of a mitochondrial gene called PTCD1 results in adult-onset obesity and fatty liver disease.

AsianScientist (Aug. 24, 2017) – In a study published in Science Advances, scientists in Australia have discovered that obesity and metabolic dysfunction are linked to a gene defect in mitochondria, the power generators of cells.

The prevalence of obesity among Australians and most western societies has been increasing for the past 30 years. Because obesity predisposes individuals to a host of pathological conditions such as diabetes, cardiovascular disease and even cancer, there is a need to develop treatments that overcome the impact of obesity on normal body function.

During normal metabolism, dietary fats and carbohydrates are broken down to produce energy. Mitochondria, which are known as the power generators of cells, play critical roles in cellular energy balance and are involved in the breakdown of fat. Unlike other subcellular compartments, mitochondria contain genes which encode proteins necessary for their energy functions, and dysregulation of those genes can cause disease.

In this study, researchers from the University of Western Australia studied mice that had lost one of their two copies of a gene encoding for a mitchondrial protein called PTCD1. Although these haploinsufficient mice were born healthy, unlike mice completely lacking PTCD1 which did not survive to birth, they developed obesity in adulthood.

The PTCD1-deficient mice had difficulty breaking down fat, which was traced to impaired biogenesis of respiratory chain components in the mitochondria. When the researchers examined the internal organs of PTCD1-deficient mice, they found that fat had accumulated in the liver—a condition known as steatosis. They also observed cardiac hypertrophy, which indicated the development of cardiovascular disease.

Importantly, the scientists discovered that PTCD1 controls the shape of mitochondria. The mitochondria of cells with reduced expression of PTCD1 were less connected and, consequently, less effective at performing their metabolic functions.

“If mitochondria are compromised or damaged, the breakdown of fat and carbohydrates is poorly regulated, which can lead to adult-onset obesity,” said Professor Aleksandra Filipovska from the Harry Perkins Institute of Medical Research. “Healthy adults will have two copies of the PTCD1 gene, but we looked at what happens when there is only one copy, and we learned that PTCD1 is vital for the breakdown of fats and energy production. When one copy of this gene is lost, it results in obesity, fatty liver and ultimately heart disease.”

“Our new model is helping us test drugs that can lessen the burden of obesity and fatty liver disease,” said Filipovska.

The article can be found at: Perks et al. (2017) Adult-onset Obesity is Triggered by Impaired Mitochondrial Gene Expression.


Source: University of Western Australia; Photo: Shutterstock.
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