Lipolysis-driven communication between adipose tissue and liver: a key axis in metabolic regulation
- 1Department of Integrative Biology and Physiology, University of California, Los Angeles, USA
- 2For correspondence: Claudio J. Villanueva
Abstract
The adipose–liver axis is central to controlling systemic energy homeostasis, with free fatty acids (FFAs) acting as critical metabolic signals that coordinate lipid metabolism between these organs. Under physiological conditions like fasting, FFAs released via adipocyte lipolysis are taken up by the liver to support β-oxidation for ketogenesis, triglyceride synthesis, and lipoprotein production. However, in obesity and insulin resistance, chronic elevation of lipolysis exceeds hepatic lipid-handling capacity, contributing to metabolic dysfunction-associated steatotic liver disease (MASLD), lipotoxicity, and inflammation. To manage fluctuating lipid loads, hepatocytes undergo dynamic organelle remodeling—particularly within mitochondria, the endoplasmic reticulum (ER), and peroxisomes—to orchestrate lipid oxidation, storage, and detoxification. These processes are tightly regulated by transcriptional programs involving nuclear receptors (e.g., PPARα, HNF4α, and LXR) and stress-responsive signaling pathways (e.g., ATF6, XBP1, and CHOP). While these adaptive networks maintain metabolic balance under stress, their dysregulation drives hepatic dysfunction in metabolic disease. Elucidating the molecular crosstalk and regulatory mechanisms that govern this shift from adaptation to dysfunction is essential to understanding the pathogenesis of liver disease in metabolic disorders. This review highlights the molecular mechanisms underlying adipose-liver communication, the role of organelle plasticity in hepatic lipid metabolism, and the transcriptional circuits that integrate these responses.
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BibTeX
@article{zhang2026lipolysisdriven,
title = {{Lipolysis-driven communication between adipose tissue and liver: a key axis in metabolic regulation}},
author = {Sicheng Zhang and Lucydalila Cedillo and Claudio J. Villanueva},
journal = {Journal of Lipid Research},
year = {2026},
month = nov,
doi = {10.1016/j.jlr.2026.101150},
url = {https://doi.org/10.1016/j.jlr.2026.101150},
note = {CC BY},
}
RIS
TY - JOUR
TI - Lipolysis-driven communication between adipose tissue and liver: a key axis in metabolic regulation
AU - Sicheng Zhang
AU - Lucydalila Cedillo
AU - Claudio J. Villanueva
PY - 2026
DA - 2026/11/04
JO - Journal of Lipid Research
DO - 10.1016/j.jlr.2026.101150
UR - https://doi.org/10.1016/j.jlr.2026.101150
AB - The adipose–liver axis is central to controlling systemic energy homeostasis, with free fatty acids (FFAs) acting as critical metabolic signals that coordinate lipid metabolism between these organs. Under physiological conditions like fasting, FFAs released via adipocyte lipolysis are taken up by the liver to support β-oxidation for ketogenesis, triglyceride synthesis, and lipoprotein production. However, in obesity and insulin resistance, chronic elevation of lipolysis exceeds hepatic lipid-handling capacity, contributing to metabolic dysfunction-associated steatotic liver disease (MASLD), lipotoxicity, and inflammation. To manage fluctuating lipid loads, hepatocytes undergo dynamic organelle remodeling—particularly within mitochondria, the endoplasmic reticulum (ER), and peroxisomes—to orchestrate lipid oxidation, storage, and detoxification. These processes are tightly regulated by transcriptional programs involving nuclear receptors (e.g., PPARα, HNF4α, and LXR) and stress-responsive signaling pathways (e.g., ATF6, XBP1, and CHOP). While these adaptive networks maintain metabolic balance under stress, their dysregulation drives hepatic dysfunction in metabolic disease. Elucidating the molecular crosstalk and regulatory mechanisms that govern this shift from adaptation to dysfunction is essential to understanding the pathogenesis of liver disease in metabolic disorders. This review highlights the molecular mechanisms underlying adipose-liver communication, the role of organelle plasticity in hepatic lipid metabolism, and the transcriptional circuits that integrate these responses.
SN - 0022-2275
SN - 1539-7262
ER -