Apolipoprotein A5 deficiency aggravates high-fat diet-induced obesity due to impaired central regulation of food intake.

S.A. van den Berg, M.M. Heemskerk, J.J. Geerling, J.B. van Klinken, F.G. Schaap, S. Bijland, J.F. Berbee, V.J. van Harmelen, A.C. Pronk, M. Schreurs, L.M. Havekes, P.C. Rensen, K.W. van Dijk

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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.-Van den Berg, S. A. A., Heemskerk, M. M., Geerling, J. J., van Klinken, J.-B., Schaap, F. G., Bijland, S., Berbee, 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.
Original languageEnglish
Pages (from-to)3354-3362
Number of pages9
JournalFaseb Journal
Volume27
Issue number8
DOIs
Publication statusPublished - Aug 2013

Keywords

  • APOA5
  • central nervous system
  • hyperphagia
  • triglyceride metabolism
  • CENTRAL-NERVOUS-SYSTEM
  • DENSITY LIPOPROTEIN-TRIGLYCERIDE
  • INSULIN-SENSITIVE MICE
  • BLOOD-BRAIN-BARRIER
  • LDL-RECEPTOR
  • IN-VITRO
  • CARDIOVASCULAR-DISEASE
  • RICH LIPOPROTEINS
  • GENE-EXPRESSION
  • LIPID DROPLETS

Cite this

van den Berg, S. A., Heemskerk, M. M., Geerling, J. J., van Klinken, J. B., Schaap, F. G., Bijland, S., Berbee, J. F., van Harmelen, V. J., Pronk, A. C., Schreurs, M., Havekes, L. M., Rensen, P. C., & van Dijk, K. W. (2013). Apolipoprotein A5 deficiency aggravates high-fat diet-induced obesity due to impaired central regulation of food intake. Faseb Journal, 27(8), 3354-3362. https://doi.org/10.1096/fj.12-225367