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Sexually Dimorphic Kisspeptin/Receptor Dysregulation in the Reproductive White Adipose Tissue of BPH/5 Mice, A Model of Preeclampsia
Author(s) -
Gomes Viviane,
Crissman Kassandra,
Beckers Kalie,
Garcia Alexandra,
Sones Jenny
Publication year - 2021
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.2021.35.s1.03857
Subject(s) - endocrinology , medicine , adipose tissue , white adipose tissue , dyslipidemia , kisspeptin , adipokine , biology , obesity , sexual dimorphism , hypothalamus , leptin
Preeclampsia (PE) is a devastating gestational syndrome responsible for maternal and fetal morbidity/mortality. Maternal obesity and dyslipidemia are PE risk factors and adipokines may play a central role in the etiopathogenesis. Features of PE are spontaneously recapitulated by the blood pressure high subline 5 (BPH/5) mouse, including hypertension, obesity, and dyslipidemia in females before and throughout pregnancy. We have reported a sexually dimorphic phenotype in adult BPH/5: females are hyperphagic and overweight with increased reproductive white adipose tissue (rWAT), while males have similar food intake, body weight (BW) and rWAT mass as controls. Moreover, BPH/5 fed a 25% calorie restricted diet (CR) during the first 7 days (d) of gestation have reduced BW, rWAT mass, and ameliorated inflammatory milieu and adverse pregnancy outcomes. Kisspeptins (KP) are small peptides originated from the Kiss1 gene. Dysregulation of Kiss1 and the KP receptor ( Kiss1r) have been suggested in PE. Similarly, BPH/5 have Kiss1/Kiss1r misexpression at the maternal‐fetal interface. Besides their role in the hypothalamus and placenta, Kiss1/Kiss1r are also expressed in adipose tissue, with potential roles in metabolism, energy expenditure, thermoregulation and adipogenesis. When fed normal diet, adult female kiss1r ‐knockout (KO) mice have reduced energy expenditure, increased adiposity and BW, while adult male Kiss1r‐ KO have increased adiposity but similar BW than wild‐type littermates. Hence, we aimed to characterize Kiss1/Kiss1r expression in the rWAT of adult male and non‐pregnant female BPH/5. It was hypothesized that rWAT Kiss1/Kiss1r mRNA expression will be lower in the obese females when compared to control C57, but not different between adult male BPH/5 and C57. Furthermore, feeding a 25% CR diet for 7 days to non‐pregnant BPH/5 females was expected to attenuate Kiss1/Kiss1r downregulation. To test our hypothesis, rWAT was collected from adult ad libitum‐fed BPH/5 and C57 males (n=3‐4/group), non‐pregnant females (n = 5‐6/group) and BPH/5 non‐pregnant females after 7 d of 25% CR (n = 5‐6/group). Kiss1/Kiss1r mRNA was measured using RT‐PCR and comparisons were made using independent samples t‐test (SPSS) with significance at p < 0.05. Non‐pregnant adult BPH/5 females had 55‐ and 1.5‐fold lower Kiss1 and Kiss1r in rWAT, respectively, when compared to C57 (p < 0.05). In males, rWAT Kiss/Kiss1r levels were not different between BPH/5 and C57 (p > 0.05). There was no difference in Kiss1r rWAT in BPH/5 females fed ad libitum vs. 25% CR diet (p > 0.05). However, rWAT Kiss1 expression was 16‐fold higher in 25% CR BPH/5 than BPH/5 fed ad libitum (p < 0.05). In conclusion, there is a sexual dimorphism in rWAT Kiss1/Kiss1r expression in BPH/5 mice, with lower levels associated with the obese phenotype of females. When fed a 7d 25% CR diet, rWAT Kiss1 levels increase, which may be associated with the reduced BW and adiposity seen in these females. Further studies are needed to investigate the KP‐associated pathways in the adipose tissue of the PE‐like BPH/5 mouse and its potential role in maternal obesity‐related risk of developing PE.