Sexual dimorphism in offspring glucose-sensitive hypothalamic gene expression and physiological responses to maternal high-fat diet feeding

Laura Dearden, Nina Balthasar

Research output: Contribution to journalArticle (Academic Journal)peer-review

37 Citations (Scopus)

Abstract

A wealth of animal and human studies demonstrate that early life environment significantly influences adult metabolic balance, however the etiology for offspring metabolic misprogramming remains incompletely understood. Here, we determine the effect of maternal diet per se on offspring sex-specific outcomes in metabolic health and hypothalamic transcriptome regulation in mice. Furthermore, to define developmental periods of maternal diet misprogramming aspects of offspring metabolic balance, we investigated offspring physiological and transcriptomic consequences of maternal high-fat/high-sugar diet feeding during pregnancy and/or lactation. We demonstrate that female offspring of high-fat/high-sugar diet-fed dams are particularly vulnerable to metabolic perturbation with body weight increases due to postnatal processes, whereas in utero effects of the diet ultimately lead to glucose homeostasis dysregulation. Furthermore, glucose- and maternal-diet sensitive gene expression modulation in the paraventricular hypothalamus is strikingly sexually dimorphic. In summary, we uncover female-specific, maternal diet-mediated in utero misprogramming of offspring glucose homeostasis and a striking sexual dimorphism in glucose- and maternal diet-sensitive paraventricular hypothalamus gene expression adjustment. Notably, female offspring metabolic vulnerability to maternal high-fat/high-sugar diet propagates a vicious cycle of obesity and type 2 diabetes in subsequent generations.

Original languageEnglish
Pages (from-to)2144-54
Number of pages11
JournalEndocrinology
Volume155
Issue number6
DOIs
Publication statusPublished - Jun 2014

Keywords

  • Adiposity
  • Animals
  • Body Weight
  • Diet, High-Fat
  • Female
  • Gene Expression Regulation
  • Glucose
  • Hypothalamus
  • Insulin
  • Male
  • Mice
  • Sex Characteristics
  • Sweetening Agents
  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint

Dive into the research topics of 'Sexual dimorphism in offspring glucose-sensitive hypothalamic gene expression and physiological responses to maternal high-fat diet feeding'. Together they form a unique fingerprint.

Cite this