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Sex difference in the patho‐physiological consequences of adipocyte PRR deficiency
Author(s) -
Gatineau Eva,
Cohn Dianne,
Liu Yongshi,
Gong Ming,
Yiannikouris Frédérique
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.691.7
Subject(s) - endocrinology , adipocyte , medicine , adipose tissue , obesity , biology , fat pad , lipodystrophy , population , adiponectin , insulin resistance , immunology , environmental health , human immunodeficiency virus (hiv) , antiretroviral therapy , viral load
and objectives The epidemic of obesity is currently affecting more than 30% of the population in the United States. Obesity increased the expression of the (pro)renin receptor (PRR), a component of the renin‐angiotensin system, in adipose tissue. In male mice, the deletion of adipocyte PRR prevented the development of obesity and the accumulation of fat mass. However, similar to mouse model with lipodystrophy and mouse model with obesity, adipocyte‐PRR deficient ( PRR Adi/Y ) mice are characterized by a fatty liver and by an elevated systolic blood pressure (SBP). Sex‐related differences in factors associated with obesity exist between male and females, therefore the objective of our study was to determine whether the remarkable phenotype of the male PRR Adi/Y mice was sustained in female. Methods and results Male PRR Adi/Y mice expressing adiponectin‐driven Cre recombinase were bred with female mice PRR fl/fl to generate female control ( PRR fl/fl ) and adipocyte‐PRR deficient mice ( PRR Adi ). Female mice were fed a standard diet (SD) or a high fat diet (HF) for 23 weeks (n=6–13/groups). Body weight was measured weekly, body composition monthly and blood pressure by radiotelemetry at the end of the study. The deletion of adipocyte PRR in females did not change body weight (BW) curves in SD‐fed mice, but prevented the development of high fat diet‐induced obesity. Interestingly, the resistance to obesity in female mice was less pronounced than in male mice. Similar to males, the deletion of adipocyte PRR in female mice decreased by over 85% adipose tissue mass (SD: PRR fl/fl , 4.4±0.7 g; PRR Adi , 1.7±0.05 g and HF: PRR fl/fl , 5.8±1.2 g; PRR Adi , 0.6± 0.1; P<0.05). Similar to males, female PRR Adi mice developed hepatomegaly (SD: PRR fl/fl , 1.3 ± 0.1 g; PRR Adi , 2.6 ± 0.1 g, P<0.05) associated with an increase of neutral lipid contents in livers of female PRR Adi compared to control mice. At 22 weeks, radiotelemetry devices were implanted in female mice. In contrast to males, the increase in systolic blood pressure was not significantly different in SD‐fed PRR Adi female mice ( PRR fl/fl , 129 ± 3 mmHg; PRR Adi , 141 ± 9 mmHg) suggesting a sex difference in PRR mediated‐regulation of blood pressure. Blood pressure measurement in HF‐fed mice are under investigation. Conclusion In contrast to males, our results demonstrated that, elevation of blood pressure due to adipocyte PPR deficiency is abolished in female mice. Future studies will define whether sex difference in blood pressure regulation mediated by PRR depends on the renin angiotensin system and on hormonal regulation. Similar to male mice, adipocyte PRR deficiency prevents the development of obesity and decreases fat mass in female mice. Future studies will determine the mechanism by which PRR regulates lipid metabolism.