Neonatal overnutritional programming impairs the hypophagia and neuron activation induced by acute lipopolysaccharide in adult male rats

ABSTRACT

Nutritional status during critical windows in early development can challenge metabolic functions and physiological responses to immune stress in adulthood, such as the systemic inflammation induced by lipopolysaccharide (LPS). The aim of this study was to investigate the long-term effects of post-natal over- and undernutrition on the anorexigenic effect of LPS and its association with neuronal activation in the brainstem and hypothalamus of male rats. Animals were raised in litters of 3 (small – SL), 10 (normal – NL), or 16 (large – LL) pups per dam. On post-natal day 60, male rats were treated with LPS (500 µg/Kg) or vehicle for the evaluation of food intake and c-Fos expression in the area postrema (AP), nucleus of solitary tract (NTS), and paraventricular (PVN), arcuate (ARC), ventromedial (VMH), and dorsomedial (DMH) nuclei of the hypothalamus. SL, NL, and LL animals showed a decreased food consumption after LPS treatment. In under- and normonourished animals, peripheral LPS induced an increase in neuronal activation in the brainstem, PaV, PaMP, and ARC and a decrease in the number of c-Fos-ir neurons in the DMH. Overnourished rats showed a reduced hypophagic response, lower neuron activation in the NTS and PaMP, and no response in the DMH induced by LPS. These results indicate that early nutritional programming displays different responses to LPS, by means of neonatal overnutrition decreasing LPS-mediated anorexigenic effect and neuronal activation in the NTS and hypothalamic nuclei.

KEYWORDS:

• Inflammation
• endotoxin
• food intake
• hypothalamic nuclei
• brainstem
• overfeeding
• undernutrition
• c-Fos

Data availability statement

The data that support the findings of this study are available from the corresponding author, [author initials], upon reasonable request.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

Notes on contributors

Ana Luiza Wunderlich

Ana Luiza Wunderlich has recently obtained her PhD (2023) in Physiological Science from the Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil.

Larissa Stopa

Larissa Stopa is PhD student in Physiological Science at the Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil.

Andressa Busetti Martins

Andressa Busetti Martins obtained her PhD, in 2022, in Physiological Science from Multicentric Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil.

Camila Franciele de Souza

Camila Franciele de Souza has recently obtained her PhD (2023) in Physiological Science from Multicentric Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil.

Érica Monteiro

Érica Monteiro got her undergraduation in Pharmacy at the State University of Londrina in 2022.

Danielly Aguiar

Daniely Aguiar is PhD student in Physiological Science at the Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil.

Rhauany Guergolette

Rhauany Guergolette is PhD student in Physiological Science at the Postgraduate Program in Physiological Sciences, State University of Londrina, Londrina, Brazil.

Polyana Shishido

Polyana Shishido is master student in Physiological Science at the Laboratory of Neuroendocrine Physiology and Metabolism, State University of Londrina.

Cassia Thais Zaia

Cássia Thaïs Zaia is senior professor at the Department of Physiological Sciences of the State University of Londrina. She obtained her PhD in Neuroendocrine Physiology from the Federal University of Sao Paulo in 1991. Then, she worked at the Laboratory of Neuroendocrinology of the Rockefeller University, as a postdoctoral researcher for 2 years. Since 1985 she has worked at the Department of Physiological Sciences, State University of Londrina, as Professor and researcher. Her work focuses on central control of food intake and energy metabolism.

Ernane Uchoa

Ernane Uchoa is associate professor at the Department of Physiological Sciences of the State University of Londrina. He obtained his PhD in Physiology from the Medical School of Ribeirao Preto of the University of São Paulo in 2011. From 2011 to 2014, he did his postdoctoral researches at the Medical School of Ribeirao Preto of the University of Sao Paulo. In 2014, he joined the Department of Physiological Sciences, State University of Londrina, as Professor and researcher. His work focuses on neuroendocrine regulation of reproduction and energy homeostasis.