Nature communicationsAug 26, 2025

Helicobacter hepaticus may cause liver fat buildup by triggering mitochondrial stress and changing fat metabolism

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jan 20, 2026

Abstract

from Helicobacter hepaticus is associated with lipid deposition in liver cells.

H. hepaticus infection or CdtB overexpression leads to lipid accumulation in liver cells, observed in both live animals and laboratory settings.
CdtB translocates to mitochondria, where it interacts with ATP5A1 and reduces the activity of mitochondrial respiratory complex V.
Disruption of mitochondrial function by CdtB is linked to altered lipid metabolism in hepatocytes.
The mechanism of CdtB-induced lipogenesis involves a pathway that includes mitochondrial reactive oxygen species, mTORC1, and SREBP1.
Neutralizing CdtB reduces liver fat accumulation in mice infected with H. hepaticus.
Detection of H. hepaticus nucleic acid in liver tissues of some patients with metabolic dysfunction-associated liver disease () indicates a possible connection between the infection and MASLD progression.

Simplified

Host-pathogen interaction influences many non-infectious diseases, including metabolic diseases. Helicobacter hepaticus (H. hepaticus) has been found in some metabolic dysfunction-associated steatotic liver disease () patients, however, the causal link and underlying mechanisms remain unclear. Here we report that H. hepaticus infection or overexpression of of H. hepaticus induces lipid deposition in hepatocytes, both in vivo and in vitro. Furthermore, we identify that CdtB translocates to mitochondria with the help of Hsp90, interacts with ATP5A1, reduces mitochondrial respiratory complex V activity, damages mitochondria, and disrupts lipid metabolism. Mechanistically, CdtB-induced lipogenesis depends on the CdtB-mitochondrial ROS-mTORC1-SREBP1 axis and CdtB-mediated NONO expression to enhance nuclear localization of SREBP1 that promote the de novo fatty acid synthesis in the hepatocytes. Neutralization of CdtB significantly alleviates hepatic lipidosis in mice upon H. hepaticus infection. Furthermore, the nucleic acid of H. hepaticus has been detected in the liver tissues of some patients with MASLD, which suggests a certain correlation between liver infection with H. hepaticus and the occurrence and progression of MASLD. Our findings highlight the critical role of CdtB in the pathogenesis of H. hepaticus infection-induced hepatic lipidosis and its potential as a therapeutic target.

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Competing interests

Competing interests: The authors declare no competing interests.

PubMed

Helicobacter hepaticus may cause liver fat buildup by triggering mitochondrial stress and changing fat metabolism

Abstract

Full Text

Funding

Competing interests

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