Obesity in adulthood and fatty liver disease may be linked to impaired function of a mitochondrial gene called Ptcd1, a mouse study suggests.
The research, “Adult-onset obesity is triggered by impaired mitochondrial gene expression,” was published in the journal Science Advances.
Mitochondrial genes are essential for regulating energy production in our cells, but how these genes influence our body physiology and metabolism is still largely unknown.
Researchers at the University of Western Australia studied mice that carry only one copy of the gene that encodes the mitochondrial protein PTCD1. While mice without either of the two gene copies for this protein died before birth, those carrying only one copy of the PTCD1 gene were healthy until adulthood, when they became obese.
When they team performed further analysis to understand the mechanisms underlying the obesity, they discovered that the mice had difficulty breaking down fat. Looking at the animals’ internal organs, the researchers found that fat had accumulated in the liver, instead of being processed, a condition known as steatosis.
In addiiton, PTCD1-deficient mice developed cardiac hypertrophy, or thickening of the heart muscle.
These physiological and metabolic impairments, scientists found, were linked to changes in mitochondria’s shape. Specifically, the organelles became less connected and, consequently, less capable of 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,” Dr. Aleksandra Filipovska, a professor at the Harry Perkins Institute of Medical Research, who was the lead author of the study, said in a press release. “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.”
The findings suggested that changes in mitochondrial gene expression can trigger long-term metabolic alterations.
“Our new model is helping us test drugs that can lessen the burden of obesity and fatty liver disease,” Filipovska said.