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Apolipoprotein A5 deficiency aggravates high-fat diet-induced obesity due to impaired central regulation of food intake.
MedLine Citation:
PMID:  23650188     Owner:  NLM     Status:  Publisher    
Mutations in apolipoprotein A5 (APOA5) have been associated with hypertriglyceridemia in humans and mice. This has been attributed to a stimulating role for APOA5 in lipoprotein lipase-mediated triglyceride hydrolysis and hepatic clearance of lipoprotein remnant particles. However, because of the low APOA5 plasma abundance, we investigated an additional signaling role for APOA5 in high-fat diet (HFD)-induced obesity. Wild-type (WT) and Apoa5(-/-) mice fed a chow diet showed no difference in body weight or 24-h food intake (Apoa5(-/-), 4.5±0.6 g; WT, 4.2±0.5 g), while Apoa5(-/-) mice fed an HFD ate more in 24 h (Apoa5(-/-), 2.8±0.4 g; WT, 2.5±0.3 g, P<0.05) and became more obese than WT mice. Also, intravenous injection of APOA5-loaded VLDL-like particles lowered food intake (VLDL control, 0.26±0.04 g; VLDL+APOA5, 0.11±0.07 g, P<0.01). In addition, the HFD-induced hyperphagia of Apoa5(-/-) mice was prevented by adenovirus-mediated hepatic overexpression of APOA5. Finally, intracerebroventricular injection of APOA5 reduced food intake compared to injection of the same mouse with artificial cerebral spinal fluid (0.40±0.11 g; APOA5, 0.23±0.08 g, P<0.01). These data indicate that the increased HFD-induced obesity of Apoa5(-/-) mice as compared to WT mice is at least partly explained by hyperphagia and that APOA5 plays a role in the central regulation of food intake.-Van den Berg, S. A. A., Heemskerk, M. M., Geerling, J. J., van Klinken, J.-B., Schaap, F. G., Bijland, S., Berbée, J. F. P., van Harmelen, V. J. A., Pronk, A. C. M., Schreurs, M., Havekes, L. M., Rensen, P. C. N., van Dijk, K. W. Apolipoprotein A5 deficiency aggravates high-fat diet-induced obesity due to impaired central regulation of food intake.
Sjoerd A A van den Berg; Mattijs M Heemskerk; Janine J Geerling; Jan-Bert van Klinken; Frank G Schaap; Silvia Bijland; Jimmy F P Berbée; Vanessa J A van Harmelen; Amanda C M Pronk; Marijke Schreurs; Louis M Havekes; Patrick C N Rensen; Ko Willems van Dijk
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-5-6
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  -     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-5-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
*Department of Human Genetics, †Einthoven Laboratory for Experimental Vascular Medicine, and ‡Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands;
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