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

doi:10.1016/j.jlr.2023.100434

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

J Lipid Res. 2024 Feb;65(2):100434. doi: 10.1016/j.jlr.2023.100434. Epub 2023 Aug 26.

Affiliations

¹ Department of Integrative Biology and Physiology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
² UCLA Lipidomics Lab, Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
³ Department of Biological Chemistry, Center for Epigenetics and Metabolism, Chao Family Comprehensive Cancer Center, University of California, Irvine (UCI), Irvine, CA, USA.
⁴ Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
⁵ Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, PA, USA.
⁶ Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
⁷ Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, UT, USA.
⁸ 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.
⁹ 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.
¹⁰ 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. Electronic address: cvillanueva@ucla.edu.

Abstract

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.

Keywords: Adipocytes; Adipose tissue triglyceride lipase; Ceramides; Fasting; Lipase; Lipid droplets; Lipidomics; Lipids; Liver; Triglycerides.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adipocytes / metabolism
Adipose Tissue / metabolism
Animals
Fatty Acids, Nonesterified* / metabolism
Lipidomics
Lipolysis* / physiology
Liver / metabolism
Mice
Triglycerides / metabolism

Substances

Fatty Acids, Nonesterified
Triglycerides

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

Authors

Affiliations

Abstract

Publication types

MeSH terms

Substances

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