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Motilin stimulates preadipocyte proliferation and differentiation and adipocyte lipid storage.
MedLine Citation:
PMID:  21771971     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background: Motilin is a circulating gastrointestinal peptide secreted primarily by duodenal mucosal M cells and recognized for its prokinetic effects on gastrointestinal tissues. Little information is available regarding effects on insulin/glucose homeostasis or adipocyte function. Aim: To evaluate the effects of motilin on adipocyte proliferation, differentiation, lipolysis and macronutrient uptake in adipocytes. Methods: 3T3-L1 cells and primary rat adipocytes were treated acutely and chronically with varying motilin concentrations and effects were compared to vehicle alone (control), set as 100% for all assays. Results: In preadipocytes, motilin stimulated proliferation ((3)H-thymidine incorporation) and mitochondrial activity (up to 141%±10%,p<0.001 and 158%±10%, p<0.001, respectively), in a concentration-dependent manner. Chronic supplementation with motilin during differentiation further increased lipogenesis (Oil red O staining 191±27%, p<0.05) and was associated with an up-regulation of PPAR-γ (148±8%, p<0.01), C/EBPα (142±17%, p<0.05) and Cav3 (166±20%, p<0.05) expression. In mature 3T3-L1 adipocytes motilin increased fatty acid uptake/incorporation (up to 202±12%; p<0.01), glucose uptake (up to 146±9% p<0.05) and decreased net fatty acid release (maximal -31%; p<0.05) without influencing total lipolysis (glycerol release). Similar effects were obtained in primary rat adipocytes. Motilin acutely increased expression of PPAR-γ, CEBPβ, DGAT1 and CD36, while decreasing adiponectin mRNA and secretion. In human adipose tissue, motilin receptor GPR38 correlated with HOMA-IR and GHSR1 (r=0.876, p<0.0001). Motilin binding and fatty acid incorporation into adipocytes were inhibited by antagonists MB10 and [D-lys3]-GRP6 and PI3kinase inhibitor wortmannin. Conclusion: Taken together, these results suggest that motilin may directly influence adipocyte functions by stimulating energy storage.
Authors:
Pierre Miegueu; Katherine Cianflone; Denis Richard; David H St-Pierre
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-19
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  -     ISSN:  1522-1555     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Laval University.
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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