Obesity-Induced MASLD Is Reversed by Capsaicin via Hepatic TRPV1 Activation

Area of Science:

• Hepatology
• Metabolic Disorders
• Pharmacology

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive liver condition linked to obesity and type 2 diabetes.
• Untreated MASLD can lead to severe liver damage, including cirrhosis and cancer.

Purpose of the Study:

• To investigate the potential of dietary capsaicin (CAP) in preventing high-fat diet (HFD)-induced MASLD.
• To elucidate the underlying mechanisms of CAP's action in the liver.

Main Methods:

• C57BL/6 mice were fed a high-fat diet (HFD) with or without capsaicin (CAP) for 26 weeks.
• Evaluated CAP's effects on hepatic fat accumulation, inflammation, and mitochondrial function.
• Utilized wild-type and TRPV1 knockout mice to assess the role of TRPV1 signaling.

Main Results:

• Dietary CAP prevented HFD-induced hepatic steatosis, inflammation, and insulin resistance.
• CAP activated hepatic TRPV1, leading to increased calcium influx, AMPK activation, and enhanced mitochondrial function.
• Beneficial effects were dependent on TRPV1 expression, as TRPV1 knockout mice did not show improvements.

Conclusions:

• Dietary capsaicin effectively prevents MASLD by activating hepatic TRPV1.
• TRPV1 signaling is a promising therapeutic target for managing MASLD in metabolic disorders.