Intrahepatic T cell responses modulate thermogenic adaptation in adipose tissues

Background: Activation of brown and white adipocytes occurs in response to pharmacological stimuli or cold exposure, while underlying mechanisms and metabolites remain poorly understood. Some metabolites, including bile acids, have been described to influence energy metabolism and thermogenesis in white (WAT) and brown adipose tissue (BAT). Recently, we have shown that both production and release of these metabolites into the systemic circulation are modulated by inflammation in the liver. In this study, we aim to investigate thermogenic adaptation in adipose tissues in the context of acute liver inflammation.

Methods: Using the K14-OVAp mouse model, which expresses an ovalbumin peptide sequence (SIINFEKL) on biliary epithelial cells, acute cholangitis was induced via adoptive transfer of OVA-specific OT-1 CD8+T cells. Mice were housed at different temperatures. Detection of serum transaminases, energy expenditure, mRNA expression, lipidomics as well as flow cytometric based immunophenotyping, were used to assess functional and molecular changes.

Results: Transferring OT-1 CD8+T cells triggered portal inflammation in K14-OVAp mice, demonstrated by elevated transaminase levels and increased histological inflammation (mHAI). FACS analysis confirmed recruitment of OT-1 CD8+cells to the liver and spleen. Hepatic inflammation resulted in elevated total lipid concentrations in plasma. In WAT thermogenic and lipogenic markers, like Ucp1 and Elovl3, were reduced, while BAT displayed increased energy uptake shown by significantly upregulated CD36 and Lpl gene expression.

Conclusion: Acute liver inflammation alters thermogenic responses in adipose tissue, decreasing thermogenesis in WAT and increasing energy uptake in BAT. This suggests that liver inflammation significantly impacts systemic energy metabolism.

Publication History

Article published online:
20 January 2025