Acute activation of adipocyte lipolysis reveals dynamic lipid remodeling of the hepatic lipidome

Sicheng Zhang; Kevin J. Williams; Amandine Verlande-Ferrero; Alvin P. Chan; Gino B. Su; Erin E. Kershaw; James E. Cox; John Alan Maschek; Suzanne N. Shapira; Heather R. Christofk; Thomas Q. de Aguiar Vallim; Selma Masri; Claudio J. Villanueva

Journal of Lipid Research (Feb 2024)

Acute activation of adipocyte lipolysis reveals dynamic lipid remodeling of the hepatic lipidome

Sicheng Zhang,
Kevin J. Williams,
Amandine Verlande-Ferrero,
Alvin P. Chan,
Gino B. Su,
Erin E. Kershaw,
James E. Cox,
John Alan Maschek,
Suzanne N. Shapira,
Heather R. Christofk,
Thomas Q. de Aguiar Vallim,
Selma Masri,
Claudio J. Villanueva

Affiliations

Sicheng Zhang: Department of Integrative Biology and Physiology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
Kevin J. Williams: UCLA Lipidomics Lab, Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
Amandine Verlande-Ferrero: Department of Biological Chemistry, Center for Epigenetics and Metabolism, Chao Family Comprehensive Cancer Center, University of California, Irvine (UCI), Irvine, CA, USA
Alvin P. Chan: Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
Gino B. Su: UCLA Lipidomics Lab, Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
Erin E. Kershaw: Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, PA, USA
James E. Cox: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA
John Alan Maschek: Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, UT, USA
Suzanne N. Shapira: Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
Heather R. Christofk: Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
Thomas Q. de Aguiar Vallim: Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Division of Cardiology, Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA
Selma Masri: Department of Biological Chemistry, Center for Epigenetics and Metabolism, Chao Family Comprehensive Cancer Center, University of California, Irvine (UCI), Irvine, CA, USA
Claudio J. Villanueva: Department of Integrative Biology and Physiology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; For correspondence: Claudio J. Villanueva

Journal volume & issue: Vol. 65, no. 2
p. 100434

Abstract

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Adipose tissue is the site of long-term energy storage. During the fasting state, exercise, and cold exposure, the white adipose tissue mobilizes energy for peripheral tissues through lipolysis. The mobilization of lipids from white adipose tissue to the liver can lead to excess triglyceride accumulation and fatty liver disease. Although the white adipose tissue is known to release free fatty acids, a comprehensive analysis of lipids mobilized from white adipocytes in vivo has not been completed. In these studies, we provide a comprehensive quantitative analysis of the adipocyte-secreted lipidome and show that there is interorgan crosstalk with liver. Our analysis identifies multiple lipid classes released by adipocytes in response to activation of lipolysis. Time-dependent analysis of the serum lipidome showed that free fatty acids increase within 30 min of β3-adrenergic receptor activation and subsequently decrease, followed by a rise in serum triglycerides, liver triglycerides, and several ceramide species. The triglyceride composition of liver is enriched for linoleic acid despite higher concentrations of palmitate in the blood. To further validate that these findings were a specific consequence of lipolysis, we generated mice with conditional deletion of adipose tissue triglyceride lipase exclusively in adipocytes. This loss of in vivo adipocyte lipolysis prevented the rise in serum free fatty acids and hepatic triglycerides. Furthermore, conditioned media from adipocytes promotes lipid remodeling in hepatocytes with concomitant changes in genes/pathways mediating lipid utilization. Together, these data highlight critical role of adipocyte lipolysis in interorgan crosstalk between adipocytes and liver.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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