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Desnutrin overexpression in adipocytes decreases triaclyglycerol content
Author(s) -
Duncan Robin Elaine,
Ahmadian Maryam,
Sul Hei Sook
Publication year - 2008
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.22.1_supplement.807.16
Subject(s) - lipolysis , lipid droplet , adipose triglyceride lipase , downregulation and upregulation , chemistry , medicine , endocrinology , lipase , adipose tissue , dexamethasone , adipocyte , in vitro , cytoplasm , glucagon , 3t3 l1 , enzyme , biochemistry , biology , insulin , gene
We recently identified desnutrin as a triacylglycerol (TAG) lipase that is mainly expressed in adipocytes. Desnutrin is induced by fasting when circulating levels of glucagon and glucocorticoids are elevated and lipolysis in adipocytes is high. While treatment with dibutyryl cAMP had no effect on desnutrin expression, dexamethasone caused a dose‐ and concentration‐dependent upregulation of desnutrin mRNA. Thus far, desnutrin has been shown to hydrolyze TAG in vitro, and to increase the release of free fatty acids and glycerol when overexpressed in cultured cells. However, the effect of desnutrin on TAG storage in adipocytes has not been investigated. We infected 3T3‐L1 ΔCAR adipocytes with adenoviral desnutrin‐GFP. We found that desnutrin‐GFP localized strongly to both large and small lipid droplets, and was also observed in the cytoplasm. In cells labeled with 14 C‐palmitate, desnutrin significantly increased the rate of TAG hydrolysis. Desnutrin overexpression also significantly decreased TAG content under basal conditions as well as in cells stimulated with dibutyryl cAMP. Truncation of desnutrin resulted in impaired localization, as well as a loss of activity in differentiated 3T3‐L1 cells. Our findings indicate a mechanism to explain desnutrin‐associated neutral lipid storage disorder with myopathy, and may provide a target for the development of therapeutic treatments to counter this disease.