Researchers at McMaster University have discovered that the hormone GDF15, known for reducing appetite and supporting weight loss, also plays a significant role in protecting the liver from inflammation through an unknown signaling pathway. This finding challenges the long-held belief that GDF15’s benefits are primarily tied to its effects on appetite and body weight.

The study, published in Cell Metabolism, found that GDF15 can reduce liver inflammation and slow the development of liver scarring even when weight loss does not occur. By identifying this biological pathway that directly regulates liver inflammation, future therapies could potentially target liver inflammation alongside existing treatments focused on weight and liver fat. The research involved mouse models designed to closely reproduce human MASH (metabolic dysfunction-associated steatohepatitis), using genetic, pharmacological, genomic, and spatial transcriptomics techniques to examine the effects of GDF15 activation.

GDF15 initiates signaling from the brain through the nervous system, leading to the release of glucocorticoids. These steroid hormones help suppress inflammation in the liver, with researchers observing these protective effects regardless of changes in food consumption, body weight, or liver fat. Additionally, GDF15 appeared to slow the progression of liver fibrosis, the accumulation of scar tissue that occurs as liver disease becomes more advanced. The findings suggest that GDF15 helps reprogram liver cells to reduce inflammation and scarring by shifting immune cells into a more protective and less active state, helping reduce inflammation and prevent damage to the liver.

Taken together, these two studies could help shape future therapies that specifically address liver inflammation, which is a major factor driving the progression of MASH and remains difficult to treat. Combining weight loss with inflammation control may offer new opportunities for developing more effective treatments for people living with metabolic dysfunction-associated steatohepatitis (MASH).

This is a summary. Read the original at sciencedaily.com.