Dietary-Induced Obesity and Hypothalamic Infertility in Female DBA/2J Mice

Drew V. Tortoriello, Julie McMinn, Streamson C. Chua, Jr.

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

The effects of diet and adiposity have been implicated in disturbances of female reproductive function. In an effort to better elucidate the relationship between obesity and female fertility, we analyzed the effect of increasing dietary fat content on body composition, insulin sensitivity, and pregnancy rates in two common inbred mouse strains, DBA/2J and C57BL/6J. After 16 wk, females of both strains on the high fat diet developed glucose intolerance and insulin resistance, but only the female DBA/2J mice developed dietary-induced obesity and hyperleptinemia. The high fat diet was associated with more than a 60% decrease in natural pregnancy rates of female DBA/2J mice, whereas the fertility of female C57BL/6J mice was unaffected. Despite developing a similar degree of obesity, insulin resistance, and hyperleptinemia, male DBA/2J mice did not manifest diminished fertility. Obese female DBA/2J mice achieved normal ovulatory responses and pregnancy rates after exogenous gonadotropin stimulation, suggesting their fertility defect to be central in origin. Real-time PCR quantification of hypothalamic cDNA revealed a 100% up-regulation of neuropeptide Y and a 50% suppression of GnRH expression accompanied by a 95% attenuation of leptin receptor type B expression in obese female DBA/2J mice. These findings suggest that obesity-associated hyperieptinemia, and not insulin resistance or increased dietary fat per se, gradually induces central leptin resistance, increases hypothalamic neuropeptide Y-ergic tone, and ultimately causes hypothalamic hypogonadism. The data establish high fat-fed female DBA/2J mice as a wild-type murine model of obesity-related infertility.

Original languageEnglish (US)
Pages (from-to)1238-1247
Number of pages10
JournalEndocrinology
Volume145
Issue number3
DOIs
StatePublished - Mar 2004
Externally publishedYes

Fingerprint

Female Infertility
Inbred DBA Mouse
Obesity
Insulin Resistance
Pregnancy Rate
Fertility
Dietary Fats
Neuropeptide Y
High Fat Diet
Fertility Agents
Leptin Receptors
Inbred Strains Mice
Glucose Intolerance
Hypogonadism
Adiposity
Leptin
Body Composition
Gonadotropins
Inbred C57BL Mouse
Gonadotropin-Releasing Hormone

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Dietary-Induced Obesity and Hypothalamic Infertility in Female DBA/2J Mice. / Tortoriello, Drew V.; McMinn, Julie; Chua, Jr., Streamson C.

In: Endocrinology, Vol. 145, No. 3, 03.2004, p. 1238-1247.

Research output: Contribution to journalArticle

Tortoriello, Drew V. ; McMinn, Julie ; Chua, Jr., Streamson C. / Dietary-Induced Obesity and Hypothalamic Infertility in Female DBA/2J Mice. In: Endocrinology. 2004 ; Vol. 145, No. 3. pp. 1238-1247.
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