Title
Apolipoprotein A5 deficiency aggravates high-fat diet-induced obesity due to impaired central regulation of food intake
Author
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.
Publication year
2013
Abstract
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. © FASEB.
Subject
Life
MHR - Metabolic Health Research
EELS - Earth, Environmental and Life Sciences
Biomedical Innovation
Biology
Healthy Living
APOA5
Central nervous system
Hyperphagia
Triglyceride metabolism
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http://resolver.tudelft.nl/uuid:82a6910e-b6ad-40e8-a58e-05a913393b16
DOI
https://doi.org/10.1096/fj.12-225367
TNO identifier
477623
ISSN
1530-6860
Source
FASEB Journal, 27 (8), 3354-3362
Document type
article