Brain peptides activate GH–IGF-1 axis to prevent the progression of MASLD, study reveals

Various factors including obesity, diabetes, etc. are related to the etiology of steatotic liver disease (SLD) including metabolic dysfunction-associated steatotic liver disease (MASLD) etiology and resulted in the complications in various organs. As the number of patients with SLD is increasing worldwide, it is essential to elucidate the pathological conditions and develop effective treatment methods.

The research group of Professor Kamimura in Niigata University have demonstrated the complementary role of peripheral and central nervous system on GH–IGF-1axis activation to prevent MASLD progression. IGF-1 ameliorates fatty infiltration in the liver. Its release is controlled by GH and GH activation is managed by peripheral or central nervous system. However, the role of this axis in MASLD developmental phase has not been well identified. Our study demonstrated that the GH–IGF-1 axis is significant in inhibiting the progression of MASLD. In addition to the peripheral autonomic nervous system activating gastric ghrelin to release GH, hypothalamic BDNF and CRH are keys in central nervous system for GH expression. "IGF-1 release by the nervous system is the key factor in maintaining the pathological homeostasis of MASLD, suggesting its therapeutic potential." says Prof. Kamimura.

Research results

• MASLD is a disease that causes complications in various organs in the body; however, its exact etiology is unclear and there is no definitive treatment
• We have determined that the autonomic neural pathway that connects the liver, brain, and intestines is involved in the onset and progression of MASLD.
• We have discovered that Ghrelin secreted from the stomach activates the growth hormone (GH) release from the pituitary gland through neural signal transduction, and growth hormone in the bloodstream induces insulin-like growth factor 1 (IGF-1) secretion from the hepatocytes, which suppresses the MASLD progression.
• We revealed that brain peptides activate GH–IGF-1 axis to prevent the progression of the early stages of MASLD pathology.