How Macrophage Types Influence the Development of Fatty Liver Disease? Study Sheds Light - Video

A new paper published in the journal Proceedings of National Academy of Sciences (PNAS) has revealed the intricate interaction between damaged liver cells and macrophages—a type of white blood cell responsible for eliminating harmful cells and pathogens as well as promoting normal healing.

Nonalcoholic steatohepatitis also called as metabolic dysfunction-associated steatohepatitis (MASH) is an inflammatory liver disease marked by liver scarring or fibrosis that gradually affects liver function. It significantly increases the risk of cirrhosis and liver cancer. With few treatment options available, metabolic dysfunction-associated steatohepatitis is the second leading cause of liver transplants in the United States, following cirrhosis due to chronic hepatitis C infection.

The researchers discovered that the diverse types of macrophages associated with metabolic dysfunction-associated steatohepatitis varied depending on whether the disease was worsening or improving. Crucially, they pinpointed specific macrophage subpopulations essential for addressing metabolic dysfunction-associated steatohepatitis and liver fibrosis, where scar tissue builds up and hampers the liver’s ability to function or heal. These fibrotic tissues obstruct blood flow, putting the entire organ at risk.

Looking ahead, the scientists suggest that a TREM2 agonist—a drug or substance that mimics TREM2's effects—could be helpful in treating metabolic dysfunction-associated steatohepatitis and fibrosis. It may aid in reversing metabolic dysfunction-associated steatohepatitis and fibrosis, especially when combined with lifestyle changes, weight loss, or bariatric surgery.

Reference: Ganguly S, Rosenthal SB, Ishizuka K, Troutman TD, Rohm TV, Khader N, Aleman-Muench G, Sano Y, Archilei S, Soroosh P, Olefsky JM, Feldstein AE, Kisseleva T, Loomba R, Glass CK, Brenner DA, Dhar D. Lipid-associated macrophages' promotion of fibrosis resolution during MASH regression requires TREM2. Proc Natl Acad Sci U S A. 2024 Aug 27;121(35):e2405746121. doi: 10.1073/pnas.2405746121. Epub 2024 Aug 22. PMID: 39172787.