Recent advances in understanding the role of adipocytokines during non-alcoholic fatty liver disease pathogenesis and their link with hepatokines

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is currently considered the main cause of chronic liver disease worldwide. Mechanisms leading to the development and progression of this disease are topics of great interest for researchers and clinicians. The current multi-hit hypothesis has thrown the crosstalk between liver and adipose tissue into sharp focus. It is well known that adipose tissue produces circulating factors, known as adipocytokines, which exert several effects on liver cells, promoting the onset of NAFLD and its progression to non-alcoholic steatohepatitis in obese subjects. In a similar way, hepatocytes may also respond to obesogenic stimuli by producing and releasing hepatokines into the circulation. Here, the authors provide an overview of recent advances in our understanding of the role of the most relevant adipocytokines and hepatokines in NAFLD pathogenesis, highlighting their possible molecular and functional interactions.

KEYWORDS:

• Adipocytokines
• hepatokines
• NAFLD
• adiponectin
• leptin
• resistin
• TNF-α
• IL-6
• FGF21
• fetuin-A

Financial & competing interests disclosure

This study was supported by the Italian Ministry of Health (Fondi di Ricerca Corrente) received by A Alisi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• NAFLD is a multifaceted liver disease broadly diffused worldwide.

• NAFLD pathogenesis and progression are sustained by complex interactions and mechanisms.

• The crosstalk between liver and adipose tissue mediated by hepatokines and adipocytokines is crucial for maintaining a balanced metabolic network between the two organs.

• Adipocytokines exerting metabolic and inflammatory effects in the liver show strong implications in NAFLD-related liver damage.

• Hepatocytes-derived mediators such as FGF21 and fetuin display adipocytokine-like metabolic effects, including correlation with NAFLD traits.

• FGF21 and adiponectin are a prototype of the metabolic axis between liver and adipose tissue.

• Additional experimental and clinical studies investigating the crosstalk between adipocytokines and hepatokines are needed.

• Further investigation in this field may have relevant diagnostic and therapeutic rebounds for NAFLD.