Cholesterol feeding prevents adiposity in the obese female aromatase knockout (ArKO) mouse.
The aromatase (ArKO) knockout mouse develops obesity marked by increased gonadal fat depots. This obesity is characterized by pronounced hypertrophy and hyperplasia in adipocytes with corresponding increases in transcripts involved in fat development. Aromatase deficiency in mice and humans with natural mutations of the aromatase gene also leads to metabolic syndrome, particularly hepatic steatosis. In ArKO mice, this hepatic steatosis, the increased body weight and serum triglycerides are surprisingly prevented by cholesterol feeding. We sought to investigate whether the reduction in body weight upon cholesterol feeding is reflected in gonadal fat depots, which account for a large percentage of body weight in the ArKO mouse. Indeed, gonadal fat depots in female ArKO mice were significantly reduced after cholesterol feeding. Concomitantly, adipocyte hyperplasia and hypertrophy were dramatically reduced upon cholesterol feeding in ArKO mice. Real-time PCR analysis revealed concurrent changes with adipocyte volume in the levels of lipoprotein lipase, caveolin-1 and CD59 transcripts. Little change was observed in levels of transcripts involved in de novo fatty acid synthesis, beta-oxidation, lipolysis, differentiation and cholesterol metabolism, suggesting that cholesterol feeding prevents hyperplasia and hypertrophy of ArKO adipocytes, possibly as a consequence of changes in transcript levels of lipoprotein lipase and therefore fatty acid uptake.
Misso
M L
ML
Prince Henry's Institute of Medical Research, P.O. Box 5152, Clayton 3168, Victoria, Australia. marie.misso@med.monash.edu.au
Hewitt
K N
KN
Boon
W C
WC
Murata
Y
Y
Jones
M E E
ME
Simpson
E R
ER
D017667:Adipocytes / Q000473:pathology*; D000273:Adipose Tissue / Q000201:enzymology* / Q000473:pathology; D000284:Administration, Oral; D000818:Animals; D001141:Aromatase / Q000172:deficiency / Q000502:physiology*; D001823:Body Composition / Q000235:genetics / Q000502:physiology; D001835:Body Weight; D002452:Cell Count; D048429:Cell Size; D002784:Cholesterol / Q000008:administration & dosage* / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D004967:Estrogens / Q000172:deficiency / Q000502:physiology; D005260:Female; D006066:Gonads; D006965:Hyperplasia / Q000378:metabolism / Q000517:prevention & control; D006984:Hypertrophy / Q000378:metabolism / Q000517:prevention & control; D051379:Mice; D018345:Mice, Knockout; D047495:PPAR gamma / Q000378:metabolism; D011897:Random Allocation; D018709:Statistics, Nonparametric
D004041:Dietary Fats; D004967:Estrogens; D047495:PPAR gamma; D002784:Cholesterol; D001141:Aromatase