Increased expression of hypothalamic leptin receptor and adiponectin accompany resistance to dietary-induced obesity and infertility in female C57BL/6J mice.
BACKGROUND
Obesity is strongly associated with female infertility, but the mechanisms underlying this relationship are largely unknown.


METHODS
We investigated the effect of increasing dietary fat percentage upon body mass, hypothalamic neuropeptide gene expression, adipose hormone secretion and fertility in females of the inbred mouse strains C57BL/6J and DBA/2J. To assess the effect of obesity independent of dietary influence, we also compared these parameters in wild-type female C57BL/6J mice to those congenic for the obesogenic mutations ob/ob and A(y)/a.


RESULTS
After 24 weeks, rather than exhibiting an obese, leptin-resistant phenotype like their female DBA/2J counterparts, wild-type female C57BL/6J mice remained lean, fertile and manifested increased hypothalamic LEPR-B expression. Although both mutant genotypes were associated with obesity and subfertility, ob/ob mice demonstrated significantly increased hypothalamic LEPR-B expression, whereas A(y)/a mice had a significant reduction. Interestingly, wild-type female C57BL/6J mice were noted to manifest significantly higher and lower levels of adiponectin and tissue plasminogen activator inhibitor-1 (tPAI-1), respectively, than weight-matched wild-type female DBA/2J mice.


CONCLUSIONS
We conclude that (1) resistance to the obese-infertile phenotype in female C57BL/6J mice is associated with increased hypothalamic leptin receptor expression and alterations in adipokine levels consistent with decreased adipose tissue inflammation and (2) that long-standing hyperleptinemic obesity in mice is associated with a downregulation of the hypothalamic leptin receptor.
Tortoriello
D V
DV
Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Columbia University, New York, NY 10032, USA. dt2016@columbia.edu
McMinn
J E
JE
Chua
S C
SC
D052242:Adiponectin / Q000097:blood*; D054369:Agouti-Related Protein; D000818:Animals; D001835:Body Weight; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000032:analysis; D007031:Hypothalamus / Q000737:chemistry*; D007247:Infertility, Female / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009478:Neuropeptide Y / Q000032:analysis; D009765:Obesity / Q000378:metabolism*; D011247:Pregnancy; D011333:Pro-Opiomelanocortin / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis*; D054411:Receptors, Leptin; D052243:Resistin / Q000032:analysis; D010959:Tissue Plasminogen Activator / Q000097:blood
D052242:Adiponectin; D054369:Agouti-Related Protein; D004041:Dietary Fats; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D052243:Resistin; C515447:leptin receptor, mouse; D007987:Gonadotropin-Releasing Hormone; D011333:Pro-Opiomelanocortin; D010959:Tissue Plasminogen Activator