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Effect of desacyl ghrelin, obestatin and related peptides on triglyceride storage, metabolism and GHSR signaling in 3T3‐L1 adipocytes
Author(s) -
Miegueu Pierre,
St Pierre David,
Broglio Fabio,
Cianflone Katherine
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22983
Subject(s) - obestatin , endocrinology , medicine , ghrelin , adipocyte , lipolysis , chemistry , phosphatidylinositol , adipose tissue , lipid metabolism , biology , hormone , signal transduction , biochemistry
Acyl‐ghrelin (AG), desacyl‐ghrelin (DAG) and obestatin are all derived from the same gene transcript; however their plasma levels do not necessarily change in parallel. The influence of these peptides towards the development of obesity and their direct effects on adipocyte physiology has not been thoroughly investigated. This study was designed to evaluate the direct effects of peptides of the ghrelin family on preadipocyte proliferation, differentiation and adipocyte lipid and glucose metabolism in 3T3‐L1 cells. 3T3 cells were treated with physiological peptide concentrations for 1 h to 9 days, and the relevant assays measured. In preadipocytes, AG, GHRP‐6 and DAG stimulated proliferation, measured as 3 H‐thymidine incorporation (up to 200%, P < 0.05), while all peptides stimulated differentiation (up to 300%, P < 0.01) as compared to standard differentiation conditions. In adipocytes, FA uptake was increased in a concentration‐dependent manner especially with obestatin (three‐ to fourfold, P < 0.001) and DAG (three‐ to fivefold, P < 0.001). By contrast, glucose transport was unchanged. DAG and obestatin significantly decreased lipolysis measured as non‐esterified fatty acid and glycerol release by 50%, P < 0.05–0.01 and 51%, P < 0.01, respectively. Interestingly, DAG stimulation of FA uptake was blocked with GHSR1 antagonist ( D ‐lys 3 )‐GHRP‐6 ( P < 0.05), phospholipase C inhibitor U73122 and phosphatidylinositol‐3‐kinase inhibitor wortmannin ( P < 0.001). Finally, in omental but not subcutaneous human adipose tissue, GHSR1 correlated with BMI (r = 0.549, P < 0.05) and insulin (r = 0.681, P < 0.01). Taken together, these results suggest that ghrelin‐related peptides may directly affect adipose tissue metabolism. J. Cell. Biochem. 112: 704–714, 2011. © 2010 Wiley‐Liss, Inc.