Calorie restriction protects against acute systemic LPS-induced inflammation

ABSTRACT

Caloric restriction (CR) has been proposed as a nutritional strategy to combat chronic diseases, including neurodegenerative diseases, as well as to delay aging. However, despite the benefits of CR, questions remain about its underlying mechanisms and cellular and molecular targets.

Objective: As inflammatory processes are the basis or accompany chronic diseases and aging, we investigated the protective role of CR in the event of an acute inflammatory stimulus.

Methods: Peripheral inflammatory and metabolic parameters were evaluated in Wistar rats following CR and/or acute lipopolysaccharide (LPS) administration, as well as glial changes (microglia and astrocytes), in two regions of the brain (hippocampus and hypothalamus) involved in the inflammatory response. We used a protocol of 30% CR, for 4 or 8 weeks. Serum and brain parameters were analyzed by biochemical or immunological assays.

Results: Benefits of CR were observed during the inflammatory challenge, where the partial reduction of serum interleukin-6, mediated by CR, attenuated the systemic response. In the central nervous system (CNS), specifically in the hippocampus, CR attenuated the response to the LPS, as evaluated by tumor necrosis factor alpha (TNFα) levels. Furthermore, in the hippocampus, CR increased the glutathione (GSH) levels, resulting in a better antioxidant response.

Discussion: This study contributes to the understanding of the effects of CR, particularly in the CNS, and expands knowledge about glial cells, emphasizing their importance in neuroprotection strategies.

KEYWORDS:

• Astrocyte
• caloric restriction
• inflammation
• GFAP
• Hippocampus
• LPS
• microglia
• neuroprotection

Acknowledgements

The authors thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) and National Institute of Science and Technology for Excitotoxicity and Neuroprotection (INCTEN/MS/CNPq).

Disclosure statement

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

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul; Instituto Nacional de Ciência e Tecnologia para Excitotoxicidade e Neuroproteção.

Notes on contributors

Vanessa-Fernanda da Silva

Vanessa-Fernanda da Silva degree in biology and currently biochemistry PhD student at UFRGS (Brazil).

Vitor Gayger-Dias

Vitor Gayger-Dias, degree in biology and currently biochemistry PhD student at UFRGS (Brazil).

Rafaela Sampaio da Silva

Rafaela Sampaio da Silva, undergraduate student in nutrition and scientific initiation program at UFRGS (Brazil).

Thomas Michel Sobottka

Thomas Michel Sobottka, undergraduate student in biology and scientific initiation program at UFRGS (Brazil).

Anderson Cigerce

Anderson Cigerce, degree in biology, currently MSc student in biochemistry at UFRGS (Brazil).

Lílian Juliana Lissner

Lílian Juliana Lissner, degree in chemistry, PhD in biochemistry (Brazil), currently post-doctorate in the department of Physiology and Pharmacology at the Università degli Studi di Roma “La Sapienza” (Italy).

Krista Minéia Wartchow

Krista Minéia Wartchow, degree in pharmacy, PhD in biochemistry (Brazil), currently post-doctorate in the department of Radiology, Brain Health Imaging Institute, Weill Cornell Medicine, New York (USA).

Letícia Rodrigues

Letícia Rodrigues, degree in physiotherapy, PhD in biochemistry, currently post-doctorate in Neurosciences at UFRGS (Brazil).

Caroline Zanotto

Caroline Zanotto, degree in pharmacy, PhD in biochemistry, working in the biochemistry laboratory at GHC hospital in Porto Alegre (Brazil).

Fernanda Carolina Telles da Silva Fróes

Fernanda Carolina Telles da Silva Fróes, degree in nutrition, PhD in biochemistry at UFRGS (Brazil).

Marina Seady

Marina Seady, degree in nutrition, PhD in biochemistry au UFRGS, currently research fellow in the Departments of Immunology, Mayo Clinic, Rochester (USA).

André Quincozes-Santos

André Quincozes-Santos, degree in pharmacy, PhD in biochemistry, Professor in the department of Biochemistry at UFRGS (Brazil).

Carlos-Alberto Gonçalves

Carlos-Alberto Gonçalves, MD and PhD in biochemistry, honorary member of the Cuban neuroimmunology network and head of the CNS Ca2+-binding proteins laboratory at UFRGS (Brazil).