title: Apolipoprotein A5 deficiency aggravates high-fat diet-induced obesity due to impaired central regulation of food intake.
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.
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Sjoerd A A
authors: SA
authors: van den Berg
authors: Mattijs M
authors: MM
authors: Heemskerk
authors: Janine J
authors: JJ
authors: Geerling
authors: Jan-Bert
authors: JB
authors: van Klinken
authors: Frank G
authors: FG
authors: Schaap
authors: Silvia
authors: S
authors: Bijland
authors: Jimmy F P
authors: JF
authors: Berbée
authors: Vanessa J A
authors: VJ
authors: van Harmelen
authors: Amanda C M
authors: AC
authors: Pronk
authors: Marijke
authors: M
authors: Schreurs
authors: Louis M
authors: LM
authors: Havekes
authors: Patrick C N
authors: PC
authors: Rensen
authors: Ko Willems
authors: KW
authors: van Dijk
mesh_terms: D000818:Animals; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins / Q000008:administration & dosage / Q000172:deficiency* / Q000235:genetics; D002151:Calorimetry; D059305:Diet, High-Fat / Q000009:adverse effects*; D004435:Eating / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism; D006949:Hyperlipidemias / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D006963:Hyperphagia / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*
chemical_list: C499058:Apoa5 protein, mouse; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D008055:Lipids
keywords: APOA5; central nervous system; hyperphagia; triglyceride metabolism