Fernando Bril, M.D., and colleagues recently investigated the relationship between insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD). 

Bril is an assistant professor in the UAB Division of Endocrinology, Diabetes, and Metabolism and associate scientist in the UAB Comprehensive Diabetes Center (UCDC). He has over 60 publications in the field of MASLD, Type 2 diabetes and obesity.

MASLD was formerly called nonalcoholic fatty liver disease. MASLD is the most common chronic liver disease across the globe, affecting more than 30% of the population, according to the American Association for the Study of Liver Diseases.

Specifically, researchers were interested in whether carriers of a specific variant of the PNPLA3 gene develop MASLD in the absence of insulin resistance. 

After assessing 204 participants, Bril and researchers found that insulin resistance was a fundamental feature of MASLD whether the individual had a PNPLA3 gene variant, or not.

The PNPLA3 variant has been identified as the major common genetic determinant of MASLD, according to the National Institutes of Health (NIH).

Bril and colleagues’ research resulted in the research article “Insulin resistance is an integral feature of MASLD even in the presence of PNPLA3 variants,” which was published in the peer-reviewed, scientific journal JHEP Reports. 

Authors state that the purpose of the study was to carefully assess the relationship between insulin resistance and MASLD in correlation to the variant PNPLA3 allele. 

Research methods consisted of PNPLA3 genotyping; an oral glucose tolerance test; and liver proton magnetic resonance spectroscopy and percutaneous liver biopsy, if diagnosed with MASLD.

Contrary to the thought that the PNPLA3 allele variant is associated with MASLD in the absence of insulin resistance the scientists note that based on their findings: “This calls for reframing patients with "PNPLA3 MASLD" not as insulin sensitive, but on the contrary, as an insulin-resistant population with increased hepatic susceptibility to metabolic insults, such as obesity or diabetes.”