Investigating the Role of AgRP Neurons in the Metabolic Gating of Reproduction during Caloric Restriction and Postpartum Lactation

Presenter

Keertana Gangireddy

Campus

UMass Amherst

Sponsor

Stephanie L. Padilla, Department of Biology, UMass Amherst

Schedule

Session 5, 3:30 PM - 4:15 PM [Schedule by Time][Poster Grid for Time/Location]

Location

Poster Board A61, Campus Center Auditorium, Row 4 (A61-A80) [Poster Location Map]

Abstract

Hypothalamic neurons co-expressing neuropeptide Y and agouti-related peptide (AgRP) are critical for survival and regulate food-seeking behavior. AgRP neurons are activated during negative energy balance (when energy supply is not sufficient to meet energy demands) and have been implicated in leptin associated infertility. During negative energy balance, AgRP neurons play a substantial role in metabolically gating of the reproductive axis by inhibiting Kiss1 neurons. AgRP neurons may be ablated using diphtheria toxin in transgenic mice that express the human form of the diphtheria toxin receptor (Agrp^hDtr). Ablating AgRP neurons results in lethal aphagia in adult mice, however, if AgRP neurons are ablated earlier in development (juvenile mice), animals survive and have a similar growth trajectory to non-ablated controls. In this study, we examine the effect of ablating AgRP neurons in females during two states of negative energy balance; 1) caloric restriction, and 2) lactation. We compared two cohorts of mice in which diphtheria toxin was administered to ablate AgRP neurons: 1) adult mice, and 2) adolescent mice. Consistent with previous literature, ablation of AgRP neurons in adult animals resulted in aphagia, whereas ablation of AgRP in adolescent animals did not alter feeding or survival. Our results indicate that ablating AgRP neurons during early development causes resistance to caloric restriction-associated infertility. Furthermore, there was a significant reduction in the duration of lactational infertility in post-partum AgRP-ablated animals. Our results overall implicate that AgRP neurons are critical for the metabolic gating of the reproductive axis during negative energy balance.

Keywords

reproductive axis, women's health, reproduction and energy

Research Area

Neuroscience and Cognitive Science

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