TY - JOUR
T1 - Apolipoprotein A5 deficiency aggravates high-fat diet-induced obesity due to impaired central regulation of food intake
AU - van den Berg, Sjoerd A. A.
AU - Heemskerk, Mattijs M.
AU - Geerling, Janine J.
AU - van Klinken, Jan-Bert
AU - Schaap, Frank G.
AU - Bijland, Silvia
AU - Berbee, Jimmy F. P.
AU - van Harmelen, Vanessa J. A.
AU - Pronk, Amanda C. M.
AU - Bijker-Schreurs, Marijke
AU - Havekes, Louis M.
AU - Rensen, Patrick C. N.
AU - van Dijk, Ko Willems
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.
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.
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 - The FASEB Journal
JF - The FASEB Journal
IS - 8
ER -