On the potential of group-specific component (GC) inhibition for treating metabolic disease
Year: 2026
Type: article
Abstract: Recent advances in obesity and type 2 diabetes treatment using glucagon-like peptide-1 receptor agonist (GLP1RA)-based therapeutics have enabled major improvements in the management of these metabolic disorders. However, many patients cannot tolerate side effects associated with appetite suppression, and around 10% of those adhering to treatment do not lose weight. Thus, there is a need for alternative and/or additional treatment. Here, we examine the therapeutic potential of targeting a gene called Group-specific component (GC) to treat metabolic diseases. First, we review GC’s established roles in vitamin D transport, metabolism, and inflammation, including its structure-activity relationships as well as the phenotypes associated with genetic variation in GC. Next, we summarize studies of GC-null humans and mice, which were both generally healthy and viable, demonstrating the safety of inhibiting GC. Finally, we discuss novel evidence that among mice fed a high fat diet, Gc ablation confers protection against the development of obesity and type 2 diabetes. Notably, these benefits came without reductions in food intake or lean mass, the primary drivers of GLP1RA-associated adverse effects. GC therefore represents a promising novel therapeutic target for metabolic diseases.
Authors: Richard Gill, Taiyi Kuo
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7140075031