Differential modulation of diet-induced obesity and adipocyte functionality by
human apolipoprotein E3 and E4 in mice.
Authors Arbones-Mainar JM, Johnson LA, Altenburg MK, Maeda N
Submitted By Nobuyo Maeda on 2/8/2009
Status Published
Journal International journal of obesity (2005)
Year 2008
Date Published 10/1/2008
Volume : Pages 32(10) : 1595 - 1605
PubMed Reference 18725890
Abstract OBJECTIVE: Apolipoprotein E (apoE), a key protein in lipid metabolism, is highly
expressed in adipose tissues. Studies have shown that human APOE*4 is associated
with a lower body mass index but with a greater risk of coronary heart disease
compared with other APOE alleles. To define the isoform-specific role of apoE in
regulating the expandability and functionality of adipose tissues, we
investigated the effects of diet-induced obesity in mice whose endogenous Apoe
gene has been replaced by either the human APOE*3 or APOE*4 allele. RESULTS:
After 8 weeks on a Western-type high-fat diet, male APOE4 mice displayed
impaired tolerance to glucose and fat overload compared with APOE3 mice.
Subcutaneous fat tissues in APOE4 and APOE3 mice after high fat feeding were not
different. In contrast, although epididymal fat tissues in APOE4 mice gained 30%
less weight during the high fat feeding than in APOE3 mice, they showed impaired
insulin-stimulated glucose uptake ex vivo. Epididymal APOE4 adipocytes were
larger in size than APOE3 adipocytes, and expressed reduced levels of mRNA for
peroxisome proliferator-activated receptor gamma2 and adiponectin, important
markers of adipocyte functionality. Adenoviral expression of apoE3 in apoE-null
culture adipocytes induced adiponectin mRNA in a dose-dependent manner, but the
induction was significantly blunted in cells overexpressing apoE4. However, in
contrast to the apoE3-expressing cells, Glut1, but not Glut4, expression levels
were positively correlated with increased apoE4 mRNA, suggesting that apoE4
expression in adipocyte interferes in insulin-sensing pathways. CONCLUSION:
Dysfunctional epididymal adipose tissues contribute to the accelerated
impairment of glucose tolerance in APOE4 mice fed a Western-type diet. Our
results underscore the importance of functionality of individual fat depots
rather than total fat mass as a determinant for metabolic disturbance during
diet-induced obesity.

Investigators with authorship
Nobuyo MaedaUniversity of North Carolina


Apoeapolipoprotein E
Slc1a3solute carrier family 1, member 3
Slc2a1solute carrier family 2 (facilitated glucose transporter), member 1
Slc2a4solute carrier family 2 (facilitated glucose transporter), member 4
Adipoqadiponectin, C1Q and collagen domain containing