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

doi:10.1096/fj.12-225367

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 language	English
Pages (from-to)	3354-3362
Number of pages	9
Journal	Faseb Journal
Volume	27
Issue number	8
DOIs	https://doi.org/10.1096/fj.12-225367
Publication status	Published - 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

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10.1096/fj.12-225367

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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

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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.-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.",

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",

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

year = "2013",

month = aug,

doi = "10.1096/fj.12-225367",

language = "English",

volume = "27",

pages = "3354--3362",

journal = "Faseb Journal",

issn = "0892-6638",

publisher = "FASEB",

number = "8",

}

van den Berg, SA, Heemskerk, MM, Geerling, JJ, van Klinken, JB, Schaap, FG, Bijland, S, Berbee, JF, van Harmelen, VJ, Pronk, AC, Schreurs, M, Havekes, LM, Rensen, PC & van Dijk, KW 2013, 'Apolipoprotein A5 deficiency aggravates high-fat diet-induced obesity due to impaired central regulation of food intake.', Faseb Journal, vol. 27, no. 8, pp. 3354-3362. https://doi.org/10.1096/fj.12-225367

TY - JOUR

T1 - Apolipoprotein A5 deficiency aggravates high-fat diet-induced obesity due to impaired central regulation of food intake.

AU - van den Berg, S.A.

AU - Heemskerk, M.M.

AU - Geerling, J.J.

AU - van Klinken, J.B.

AU - Schaap, F.G.

AU - Bijland, S.

AU - Berbee, J.F.

AU - van Harmelen, V.J.

AU - Pronk, A.C.

AU - Schreurs, M.

AU - Havekes, L.M.

AU - Rensen, P.C.

AU - van Dijk, K.W.

PY - 2013/8

Y1 - 2013/8

N2 - 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.

AB - 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.

KW - APOA5

KW - central nervous system

KW - hyperphagia

KW - triglyceride metabolism

KW - CENTRAL-NERVOUS-SYSTEM

KW - DENSITY LIPOPROTEIN-TRIGLYCERIDE

KW - INSULIN-SENSITIVE MICE

KW - BLOOD-BRAIN-BARRIER

KW - LDL-RECEPTOR

KW - IN-VITRO

KW - CARDIOVASCULAR-DISEASE

KW - RICH LIPOPROTEINS

KW - GENE-EXPRESSION

KW - LIPID DROPLETS

U2 - 10.1096/fj.12-225367

DO - 10.1096/fj.12-225367

M3 - Article

C2 - 23650188

SN - 0892-6638

VL - 27

SP - 3354

EP - 3362

JO - Faseb Journal

JF - Faseb Journal

IS - 8

ER -

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

Abstract

Keywords

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