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Niemann‐Pick Type C2 (NPC2) Protein Regulates Adipocyte Metabolism
Author(s) -
Frolov Andrey,
Csepeggi Chad,
Du Hong
Publication year - 2007
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.21.5.a664
Subject(s) - endocrinology , adipocyte , medicine , lipolysis , npc1 , adipogenesis , lipid droplet , lipid metabolism , cholesterol , gene silencing , chemistry , biology , adipose tissue , intracellular , microbiology and biotechnology , gene , biochemistry , endosome
NPC2 has been recently identified as the second gene in the autosomal recessive cholesterol storage disorder, the NPC disease. It encodes a secretory, 151 amino acid protein with unknown function. NPC1 encodes integral membrane protein that regulates cholesterol content in lipid droplets through mobilization of intracellular cholesterol to the plasma membrane. The NPC1 and NPC2 mutations yield similar clinical phenotypes that are characterized, among the others, by a very short lifespan (11–12 weeks) of NPC‐null mice as well as by their significant (~ 3‐fold) weight loss. The latter circumstance prompted us to investigate a role of NPC2 protein in adipogenesis and adipocyte metabolism. We report here that young, 4‐weeks old male and female NPC1‐null mice, had already developed characteristic hepatomegaly but displayed normal development and growth of both visceral and subcutaneous fat pads as revealed by immunohistochemistry. However, the siRNA silencing of NPC2 gene in adult primary human adipocytes resulted in dramatic (~ 2‐fold) reduction in their triacylglycerol pool due to activated lipolysis. The latter process was accompanied by inhibition of fatty acid transport (~3.5‐fold) and stimulation of insulin‐independent, GLUT1‐dependent glucose uptake (~2‐fold). These results identify NPC2 protein as a novel adipokine that promotes adipocyte fat accumulation and insulin sensitivity.