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Impaired mTOR Regulation of Lipolysis in Lipocalin‐2 Deficient Adipocytes
Author(s) -
Deis Jessica,
Guo Hong,
Chen Xiaoli
Publication year - 2015
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.29.1_supplement.595.17
Subject(s) - lipolysis , medicine , endocrinology , mtorc1 , pi3k/akt/mtor pathway , lipocalin , mechanistic target of rapamycin , lipid metabolism , adipocyte , biology , adipose tissue , hormone sensitive lipase , chemistry , signal transduction , microbiology and biotechnology
Mammalian target of rapamycin (mTOR) is an intracellular sensor of nutrient status and plays a key role in lipid and glucose metabolism. Rapamycin, a specific inhibitor of mTORC1, has been known to regulate lipolysis. Lipocalin 2 (Lcn2), a recently identified adipokine, has been shown to regulate lipid metabolism and non‐adrenergic thermogenesis. Herein, we assessed mTOR signaling in Lcn2 knockout (KO) adipocytes and evaluated the impact of Lcn2 deficiency on the metabolic regulation of rapamycin. 3T3‐L1 cells and inguinal stromal‐vascular cells collected from wild‐type (WT) and Lcn2 KO mice were cultured and differentiated to adipocytes. Lcn2 KO adipocytes had decreased basal lipolysis, but normal isoproterenol‐stimulated lipolysis when compared to WT adipocytes. Interestingly, 24h treatment of 3T3‐L1 adipocytes with rapamycin resulted in a marked increase in Lcn2 gene and protein expression and secretion; this effect of rapamycin was only observed in the presence of insulin. Due to the elevated response of Lcn2 expression to rapamycin, we next sought to determine the role of Lcn2 in rapamycin‐mediated lipolysis. Rapamycin induced expression of lipolytic genes such as hsl, atgl, and plin1 was completely blunted in Lcn2 KO adipocytes. Despite an impaired response to rapamycin, insulin‐stimulated mTOR signaling was not significantly altered in Lcn2 KO adipocytes. There were no significant changes in 24h insulin‐stimulated phosphorylation of p70S6 kinase and Akt at Ser473 or Thr308 in Lcn2 KO adipocytes. This suggests that the absence of Lcn2 impairs mTOR‐regulated downstream targets and processes. In conclusion, Lcn2 deficient adipocytes demonstrate an impaired response to rapamycin‐mediated lipolysis, suggesting that Lcn2 is an important mediator of mTOR regulation in lipolysis.