Researchers at McMaster University have discovered that a naturally\u00a0occurring hormone best known for suppressing appetite and promoting weight loss also helps protect the liver from inflammation through a previously unknown signaling pathway, opening new possibilities for treating advanced fatty liver disease.\u00a0<\/p>\n
The findings, published in\u00a0Cell Metabolism\u00a0on\u00a0August 10, 2026, reveal that the hormone GDF15 can suppress liver inflammation and slow the progression of liver scarring independently of weight loss – a surprising discovery that challenges longstanding assumptions about how the hormone works.\u00a0<\/p>\n
Millions of people worldwide live with metabolic dysfunction-associated steatohepatitis (MASH), a severe form of fatty liver disease<\/a> that can progress to cirrhosis, liver\u00a0cancer\u00a0and liver failure. While new weight-loss medications have improved outcomes for many patients, liver inflammation often persists even after significant weight loss. The new research\u00a0identifies\u00a0a biological pathway that helps regulate liver inflammation, suggesting future treatments may be able to complement existing weight-loss therapies.\u00a0<\/p>\n
<\/p>\n Our findings show that GDF15 does much more than regulate appetite and body weight. We discovered that GDF15 activates a natural brain-to-liver signaling pathway that helps suppress liver inflammation and reduce fibrosis. This changes how we\u00a0think about the hormone and suggests it may be part of the body’s own defense system against chronic liver injury.”\u00a0<\/p>\n
Gregory Steinberg, professor in McMaster University’s Department of Medicine, co-director of the Centre for Metabolism, Obesity and Diabetes Research (MODR), and senior author of the study<\/p>\n
<\/p>\n Using mouse models that closely mimic human MASH, researchers combined genetic, pharmacological,\u00a0genomic\u00a0and spatial transcriptomics\u00a0approaches to investigate the role of GDF15 in advanced liver disease.\u00a0They found that\u00a0GDF15\u00a0activates\u00a0signalling\u00a0from the brain to the nervous system<\/a>\u00a0that leads to the release of glucocorticoids,\u00a0a class of steroid hormones that play a vital role in metabolism, immune function, and the stress response. The glucocorticoids\u00a0help dampen inflammation in the liver and those protective effects occur independently of changes in food intake, body\u00a0weight\u00a0or liver fat.\u00a0GDF15\u00a0was also found to\u00a0help limit the progression of liver fibrosis, a buildup of scar tissue associated with advanced disease.\u00a0<\/p>\n “GDF15 helps reprogram liver cells to reduce inflammation and scarring by advanced spatial technology,” says\u00a0Dongdong Wang, first\u00a0and corresponding\u00a0author of the study and assistant professor McMaster’s Department of Medicine. “Instead of causing liver damage, GDF15 appears to help calm the liver’s immune system. It shifts immune cells into a more protective and less active state, helping reduce inflammation and prevent damage to the liver.”\u00a0<\/p>\n Research\u00a0published in 2023 from Steinberg and\u00a0Wang,showed\u00a0that GDF15 helps\u00a0maintain\u00a0calorie burning during weight loss, but the new study reveals an entirely different role for the hormone: protecting the liver through a previously unknown anti-inflammatory<\/a> pathway.\u00a0<\/p>\n Together, researchers say\u00a0the two studies\u00a0could help guide the development of future therapies aimed specifically at liver inflammation, a major driver of disease progression that\u00a0remains\u00a0difficult to treat.\u00a0<\/p>\n Steinberg, an executive member of\u00a0NexusHealth\u00a0at McMaster and chief scientific officer,\u00a0shareholder\u00a0and co-founder of\u00a0Espervita\u00a0Therapeutics,\u00a0recently co-authored preclinical research\u00a0describing a promising drug candidate for advanced liver disease. While that work focused on a potential therapeutic compound, the new study\u00a0identifies\u00a0a biological pathway the body naturally uses to suppress liver inflammation, offering new insight that could inform the next generation of treatments.\u00a0<\/p>\n “Current therapies largely focus on reducing body weight and liver fat,” says Steinberg. “Our work suggests there may be value in combining those approaches with therapies that directly target inflammation. By understanding how the body naturally protects the liver, we can identify new opportunities to develop more effective treatments for people living with MASH.”\u00a0<\/p>\n In addition to McMaster researchers, collaborators included Rune E. Kuhre and Sebastian B. J\u00f8rgensen of Novo Nordisk A\/S.\u00a0The\u00a0research was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canadian Institutes of Health Research (CIHR)\u00a0and Diabetes Canada. Novo Nordisk provided research support and supplied the GDF15 hormone used in the study.<\/p>\n Source:<\/p>\n Journal reference:<\/p>\n
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