Osaka, Japan – Researchers at Osaka University identified a degradation factor for SREBP1 as essential for maintaining the balance of saturated and unsaturated fatty acids in adipose tissue. This discovery may lead to the development of novel drugs targeting the gene ARMC5 to regulate the levels of saturated and unsaturated fatty acids in the body.

It is well-known that saturated fatty acids are detrimental to one’s health while unsaturated fatty acids are beneficial. Although most fatty acids in the body are stored in adipose tissue, the factors regulating the levels of saturated and unsaturated fatty acids in adipose tissue had remained unclear.

This research team found that the expression of stearoyl-CoA desaturase (SCD), an enzyme responsible for fatty acid desaturation, was almost completely lost in mice with adipocyte-specific deficiency of ARMC5. As a result, saturated fatty acids in adipose tissue increased, while unsaturated fatty acids decreased.

Though it was previously known that SREBP1 is activated through binding with SCAP to induce SCD expression, the team demonstrated that ARMC5 selectively degrades non-SCAP-bound SREBP1, thereby activating it.

Corresponding author Yosuke Okuno says, “ARMC5 was originally identified as a causative gene for adrenal hyperplasia, and globally, functional analyses of its role in the adrenal glands have been the main focus. In this study, however, it was revealed that ARMC5 strongly regulates the saturation level of fatty acids in adipocytes and serves as a factor that not only degrades SREBP, but also activates it.”

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The article, “ARMC5 selectively degrades SCAP-free SREBF1 and is essential for fatty acid desaturation in adipocytes,” was published in Journal of Biological Chemistry at DOI: https://doi.org/10.1016/j.jbc.2024.107953