title: Fat-specific protein 27 (FSP27) interacts with adipose triglyceride lipase (ATGL) to regulate lipolysis and insulin sensitivity in human adipocytes.
abstract: In adipocytes, lipolysis is a highly regulated process involving hormonal signals, lipid droplet-associated proteins, and lipases. The discovery of new lipid droplet-associated proteins added complexity to the current model of lipolysis. In this study, we used cultured human adipocytes to demonstrate that fat-specific protein 27 (FSP27), an abundantly expressed protein in adipocytes, regulates both basal and stimulated lipolysis by interacting with adipose triglyceride lipase (ATGL, also called desnutrin or PNPLA2). We identified a core domain of FSP27, amino acids 120-220, that interacts with ATGL to inhibit its lipolytic function and promote triglyceride storage. We also defined the role of FSP27 in free fatty acid-induced insulin resistance in adipocytes. FSP27 depletion in human adipocytes increased lipolysis and inhibited insulin signaling by decreasing AKT phosphorylation. However, reducing lipolysis by either depletion of ATGL or expression of exogenous full-length FSP27 or amino acids 120-220 protected human adipocytes against the adverse effects of free fatty acids on insulin signaling. In embryonic fibroblasts derived from ATGL KO mice, exogenous free fatty acids did not affect insulin sensitivity. Our results demonstrate a crucial role for FSP27-ATGL interactions in regulating lipolysis, triglyceride accumulation, and insulin signaling in human adipocytes.
authors.affiliation: Section of Endocrinology, Diabetes, and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Tan Hooi Min
authors.initials: THM
authors.lastname: Grahn
authors.affiliation: Section of Endocrinology, Diabetes, and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Rajween
authors.initials: R
authors.lastname: Kaur
authors.affiliation: Section of Endocrinology, Diabetes, and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Heinrichstrasse 31, A-8010 Graz.
authors.forename: Martina
authors.initials: M
authors.lastname: Schweiger
authors.affiliation: Section of Endocrinology, Diabetes, and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Vishva Mitra
authors.initials: VM
authors.lastname: Sharma
authors.affiliation: Section of Endocrinology, Diabetes, and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Mi-Jeong
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Section of Endocrinology, Diabetes, and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ido
authors.affiliation: Department of Biochemistry and Cancer Biology, University of Toledo College of Medicine, Toledo, Ohio 43614.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Smas
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Heinrichstrasse 31, A-8010 Graz.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zechner
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Heinrichstrasse 31, A-8010 Graz.
authors.forename: Achim
authors.initials: A
authors.lastname: Lass
authors.affiliation: Section of Endocrinology, Diabetes, and Nutrition, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118. Electronic address: vpuri@bu.edu.
authors.forename: Vishwajeet
authors.initials: V
authors.lastname: Puri
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance; D008049:Lipase / Q000378:metabolism*; D008066:Lipolysis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C472088:CIDEC protein, human; D007328:Insulin; D011506:Proteins; D014280:Triglycerides; D008049:Lipase
keywords: Adipocyte; Adipose Tissue Metabolism; Adipose Triglyceride Lipase; Diabetes; Diacylglycerol; Fatty Acid; Fatty Acid Metabolism; Insulin Resistance; Obesity