Fatty liver, which can lead to liver damage and disease, can occur from both overeating and starvation. Now, new research shows how cave fish, naturally resistant to hunger, unlike other animals, can protect their liver and stay healthy. The findings have implications for understanding and potentially addressing liver conditions in humans.
Researchers at the Stowers Institute for Medical Research, in collaboration with the Free University of Brussels in Belgium and Iowa State University, compared cavefish with other animals more susceptible to starvation and identified a gene responsible for the development of induced fatty liver. by starvation. The study, published in Life Sciences Alliance on March 11, 2024, led by co-authors Ansa Cobham, Ph.D., in the laboratory of research associate Nicolas Rohner, Ph.D., and Macarena Pozo-Morales, Ph.D., in the laboratory of assistant researcher El Professor Sumeet Pal Singh, Ph.D., also showed that this evolutionarily conserved gene can be targeted by an existing drug candidate to protect against liver damage.
“This same approach can be applied to what we see in overconsumption,” Rohner said. “In Western societies where too many calories and too little exercise are often a problem, this new knowledge may lead to the prevention or possible treatment of fatty liver disease.”
“We have discovered for the first time an organism, the cave fish, that can avoid fatty liver under starvation conditions,” Cobham said. “Fatty liver can lead to complications such as liver cirrhosis and liver failure. This study helps us understand more about the underlying biology of these diseases in humans.”
Cave fish are cousins of the Mexican river tetra fish that flooded underground caves more than 100,000 years ago. The researchers show that in the absence of food, cave fish in the early stages of development not only survive much longer than their river counterparts, but also do not accumulate fat in the liver.
“This was the first time we clearly demonstrated that the mechanism of this resistance is achieved by not accumulating excess fat in the liver,” Rohner said.
The accumulation of fat in liver cells causes organ damage and atrophy or wasting. The researchers compared gene expression levels between cave fish, river fish, zebra fish and even fruit flies, identifying a gene that is activated during prolonged periods of starvation in all but the cave fish.
“The expression levels of this gene are reduced in cave fish, which is a good indicator that if we are able to target this gene in humans, we will be able to treat or control human metabolic diseases such as type 2 diabetes and obesity. “Cobham said. .
The team’s findings indicate that the starvation-induced gene not only regulates fatty liver disease, but its mechanism has also been conserved from fruit flies to fish to humans, or approximately 400 million years of evolution. animal.
Protein inhibition of this gene in zebrafish and river fish larvae and deletion of the gene in fruit flies resulted in less liver fat and larger livers, indicating that this protects the liver from damage and atrophy.
“The collaboration between Dr. Sumeet Singh’s team in Belgium, our team at Stowers, and scientists at Iowa State University combined our collective expertise in zebrafish, cavefish, and fruit flies to uncover the mechanism of fatty liver.” induced by hunger,” Rohner said.