Subacute high-refined carbohydrate diet leads to abnormal reproductive control of the hypothalamic-pituitary axis in female rats

Jeanini Zimerman; Oscar M S Niño; Charles S da Costa; Jordana F Zanol; Milena Comério; Letícia N da Gama de Souza; Leandro Miranda-Alves; Rosiane A Miranda; Patrícia C Lisboa; Tays A Camilo; Rodrigo Rorato; Guilherme Andrade Alves; Renata Frazão; Helena D Zomer; Leandro C Freitas-Lima; Jones B Graceli

doi:10.1016/j.reprotox.2023.108410

Subacute high-refined carbohydrate diet leads to abnormal reproductive control of the hypothalamic-pituitary axis in female rats

Reprod Toxicol. 2023 Aug:119:108410. doi: 10.1016/j.reprotox.2023.108410. Epub 2023 May 20.

Authors

Jeanini Zimerman¹, Oscar M S Niño², Charles S da Costa¹, Jordana F Zanol¹, Milena Comério¹, Letícia N da Gama de Souza¹, Leandro Miranda-Alves³, Rosiane A Miranda⁴, Patrícia C Lisboa⁴, Tays A Camilo⁵, Rodrigo Rorato⁵, Guilherme Andrade Alves⁶, Renata Frazão⁶, Helena D Zomer⁷, Leandro C Freitas-Lima¹, Jones B Graceli⁸

Affiliations

¹ Department of Morphology, Federal University of Espírito Santo, Vitória, Brazil.
² Department of Morphology, Federal University of Espírito Santo, Vitória, Brazil; Faculty of Human Sciences and Education, Universidad de los Llanos, Villavicencio, Meta, Colombia.
³ Experimental Endocrinology Research, Development and Innovation Group, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Brazil; Postgraduate Program in Endocrinology, School of Medicine, Federal University of Rio de Janeiro, Av. Carlos Chagas Filho, Ilha do Governador, Cidade Universitária, UFRJ, RJ, Brazil.
⁴ Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, RJ, Brazil.
⁵ Department of Biophysics, Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil.
⁶ Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
⁷ Department of Physiological Sciences, University of Florida, Gainesville, FL, USA.
⁸ Department of Morphology, Federal University of Espírito Santo, Vitória, Brazil. Electronic address: jbgraceli@gmail.com.

PMID: 37211340
DOI: 10.1016/j.reprotox.2023.108410

Abstract

We previously reported that female rats placed on a diet containing refined carbohydrates (HCD) resulted in obesity and reproductive abnormalities, such as high serum LH concentration and abnormal ovarian function. However, the impacts at the hypothalamic-pituitary (HP) function, specifically regarding pathways linked to reproductive axis modulation are unknown. In this study, we assessed whether subacute feeding with HCD results in abnormal reproductive control in the HP axis. Female rats were fed with HCD for 15 days and reproductive HP axis morphophysiology was assessed. HCD reduced hypothalamic mRNA expression (Kiss1, Lepr, and Amhr2) and increased pituitary LHβ+ cells. These changes likely contribute to the increase in serum LH concentration observed in HCD. Blunted estrogen negative feedback was observed in HCD, with increased kisspeptin protein expression in the arcuate nucleus of the hypothalamus (ARH), lower LHβ+ cells and LH concentration in ovariectomized (OVX)+HCD rats. Thus, these data suggest that HCD feeding led to female abnormal reproductive control of HP axis.

Keywords: Estrogen negative feedback; High-refined carbohydrate diet; Hypothalamic-pituitary axis; Kisspeptin; LH.

MeSH terms

Animals
Arcuate Nucleus of Hypothalamus / metabolism
Carbohydrates
Diet
Female
Hypothalamus* / metabolism
Kisspeptins / genetics
Kisspeptins / metabolism
Obesity* / metabolism
Rats

Substances

Carbohydrates
Kisspeptins