Diseases impacted by metabolic dysregulation, such as liver-, kidney-, and heart diseases, share a common trait—significantly upregulated fibroblast activity. This increased fibrotic burden, called fibrosis, is a leading cause of death worldwide.

Fibrosis-specific biomarkers can help us understand fibroblast activity and, more importantly, how to regulate it, which can be the key advance our understanding of metabolic diseases and lead to more targeted and successful treatments.

Figure 1. Metabolic dysregulation and fibrosis may lead to multiple organ failure

Metabolic dysregulation is a central part of many pathologies that may lead to multiple organ failure. Usually accompanied and driven by obesity, this complex syndrome is a major cause of complications and an increased risk of outcome in various diseases.

Through the increased synthesis and deposition of extracellular matrix (ECM) proteins, fibrosis-specific biomarkers such as PRO-C3 and PRO-C6 are highly descriptive of risk of outcome in diseases affected by metabolic dysregulation.

Metabolic dysregulation causing increased levels of PRO-C3 and PRO-C6 can be observed in MAFLD/MASH (formerly NAFLD/NASH), chronic kidney disease, diabetes and heart failure, leading to impaired organ function and increased risk of adverse events as a result of increased fibroblast activity. Treatments that impact metabolic processes should therefore lead to lowered levels of particularly PRO-C3 and PRO-C6, which reflects lowered fibroblast activity, leading to risk mitigation (Figure 1).

These biomarkers can therefore be applied in patients to help accurately identify and stratify patients according to their systemic risk profile, and also be used as efficacy biomarkers. Ultimately, they can be used as tools for guiding treatment directions and monitoring patient responses to treatment. 


PRO-C6 and PRO-C3 together paint a more accurate picture of metabolic diseases, activity/progression rates, and the overall disease burden in the patient. PRO-C6 (also known as the endotrophin biomarker) and PRO-C3 are fibrosis biomarkers that measure the formation of type VI and type III collagen, respectively.

By using these biomarkers, clinicians can develop more targeted treatment plans that focus on the specific needs of each patient. This combined measurement provides unique insights into diagnosing and stratifying high-risk patients with metabolic diseases.

In addition, by monitoring the impact of treatment on PRO-C3 and PRO-C6 over time, clinicians can track disease progression and treatment efficacy, leading to more targeted and effective treatments.

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The applications presented here are for research use only.

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