Digital illustration depicting the role of Them2 in regulating fat metabolism within the liver, with a comparison of a healthy liver vs. a fatty liver.

Fatty Liver Disease: Scientists Discover a New Pathway to a Healthier Liver

Mira Elwood in Health & Wellness December 2025 • 4 min read.

"Groundbreaking research reveals how a specific enzyme could revolutionize the treatment of non-alcoholic fatty liver disease (NAFLD) and other metabolic disorders."

Non-alcoholic fatty liver disease (NAFLD) is a growing global health concern, affecting millions worldwide. This condition, often linked to obesity, poor diet, and lack of exercise, can lead to serious liver damage and other health complications. Current treatments are limited, making the search for effective interventions a top priority.

Recent research published in a leading scientific journal has brought exciting news. Scientists have uncovered a new pathway in the liver that could be key to managing NAFLD. This pathway involves a specific enzyme, called Them2, which appears to play a critical role in how the liver processes fats.

This article will explore the findings of this research, explaining the role of Them2, and how its discovery could pave the way for new treatments and lifestyle changes to combat fatty liver disease and improve overall metabolic health.

Unveiling Them2: The Liver's Gatekeeper for Fat Metabolism

Digital illustration depicting the role of Them2 in regulating fat metabolism within the liver, with a comparison of a healthy liver vs. a fatty liver.

Them2, short for Thioesterase Superfamily Member 2, is an enzyme found in the liver and other tissues. The primary function of Them2 is to regulate how fatty acids are handled within the liver cells, known as hepatocytes. Specifically, it influences how these fats are either used for energy or stored.

The study revealed that Them2 helps to channel fatty acids towards the production of triglycerides, a type of fat. These triglycerides are then packaged into very-low-density lipoproteins (VLDL), which transport fats out of the liver and into the bloodstream.

Them2 directs fatty acids towards triglyceride synthesis.
Triglycerides are packaged into VLDL particles.
VLDL transports fats out of the liver.
Dysfunction in this process can lead to fat accumulation.

When Them2 doesn't function correctly, or when there's an overabundance of fatty acids, it can lead to a build-up of fat in the liver. This accumulation is a hallmark of NAFLD, which can progress to more severe conditions like non-alcoholic steatohepatitis (NASH), cirrhosis, and even liver cancer. The discovery of Them2's role gives researchers a new target for intervention.

The Future of Liver Health: Hope on the Horizon

The discovery of Them2's role in liver health opens exciting new avenues for research and treatment. Scientists are now exploring ways to target Them2 to reduce fat accumulation in the liver, potentially preventing or reversing NAFLD and its complications. While more research is needed, this breakthrough offers a promising path toward improved liver health and overall well-being. Lifestyle changes, combined with potential targeted therapies, could be the key to fighting back against fatty liver disease.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1002/hep.30411, Alternate LINK

Title: Thioesterase Superfamily Member 2 Promotes Hepatic Vldl Secretion By Channeling Fatty Acids Into Triglyceride Biosynthesis

Subject: Hepatology

Journal: Hepatology

Publisher: Wiley

Authors: Michele Alves‐Bezerra, Yingxia Li, Mariana Acuña, Anna A. Ivanova, Kathleen E. Corey, Eric A. Ortlund, David E. Cohen

Published: 2019-03-22

Everything You Need To Know

What is the primary function of the Them2 enzyme in the liver?

Them2, or Thioesterase Superfamily Member 2, primarily regulates how fatty acids are handled within liver cells (hepatocytes). It influences whether these fats are used for energy or stored. Specifically, Them2 directs fatty acids towards the production of triglycerides, which are then packaged into very-low-density lipoproteins (VLDL) for transport out of the liver.

How does Them2 dysfunction contribute to non-alcoholic fatty liver disease (NAFLD)?

When Them2 doesn't function correctly, or when there is an overabundance of fatty acids, it can lead to a build-up of fat in the liver. This accumulation of fat is a hallmark of NAFLD. If left unchecked, NAFLD can progress to more severe conditions like non-alcoholic steatohepatitis (NASH), cirrhosis, and even liver cancer. Therefore, the proper function of Them2 is critical for maintaining liver health.

What are very-low-density lipoproteins (VLDL) and what is their relevance to Them2 and liver health?

Very-low-density lipoproteins (VLDL) are particles that transport fats, specifically triglycerides, out of the liver and into the bloodstream. Them2 plays a role in directing fatty acids toward triglyceride synthesis, which are then packaged into VLDL. If Them2 function is impaired, fat can accumulate in the liver instead of being transported out via VLDL, contributing to NAFLD.

How could the discovery of Them2's role in liver health lead to new treatments for NAFLD?

The discovery of Them2's role provides a new target for intervention. Scientists are now exploring ways to target Them2 to reduce fat accumulation in the liver, potentially preventing or reversing NAFLD and its complications. This could involve developing therapies that enhance Them2 function or that address the underlying causes of its dysfunction. Combining these potential therapies with lifestyle changes could be a powerful approach to combating fatty liver disease.

Beyond medication, what lifestyle strategies might complement Them2-targeted treatments for NAFLD?

Given that NAFLD is often linked to obesity, poor diet, and lack of exercise, lifestyle changes are crucial. A healthy diet low in processed fats and sugars, combined with regular physical activity, can help reduce the overall burden of fatty acids on the liver. These changes, alongside potential Them2-targeted therapies, could synergistically improve liver health and overall metabolic well-being by optimizing the pathways influenced by Them2.