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FSP27 interacts with ATGL to regulate lipolysis and insulin sensitivity in human adipocytes (LB60)
Author(s) -
Grahn Tan Hooi Min,
Kaur Rajween,
Yin Jun,
Schweiger Martina,
Sharma Vishva,
Lee MiJeong,
Yasuo Ido,
Smas Cynthia,
Zechner Rudolph,
Lass Achim,
Puri Vishwajeet
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb60
Subject(s) - adipose triglyceride lipase , lipolysis , perilipin , lipid droplet , medicine , endocrinology , adipose tissue , triglyceride , chemistry , insulin receptor , insulin resistance , insulin , microbiology and biotechnology , biology , cholesterol
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 the present 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). We identified a core domain of FSP27, aa 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 aa 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, TG accumulation, and insulin signaling in human adipocytes. Grant Funding Source : Supported by NIH‐NIDDK R56DK094815, NIH‐NIDDK P30DK046200, KL‐2 (8KL2TR000158)