Dietary flavonoid kaempferol reduces obesity-associated hypothalamic microglia activation and promotes body weight loss in mice with obesity

ABSTRACT

Background

Obesity results from an unbalance in the ingested and burned calories. Energy balance (EB) is critically regulated by the hypothalamic arcuate nucleus (ARC) by promoting appetite or anorectic actions. Hypothalamic inflammation, driven by high activation of the microglia, has been reported as a key mechanism involved in the development of diet-induced obesity. Kaempferol (KF), a flavonoid-type polyphenol present in a large number of fruits and vegetables, was shown to regulate both energy metabolism and inflammation.

Objectives

In this work, we studied the effects of both the central and peripheral treatment with KF on hypothalamic inflammation and EB regulation in mice with obesity.

Methods

Obese adult mice were chronically (40 days) treated with KF (0.5 mg/kg/day, intraperitoneally). During the treatment, body weight, food intake (FI), feed efficiency (FE), glucose tolerance, and insulin sensitivity were determined. Analysis of microglia activation in the ARC of the hypothalamus at the end of the treatment was also performed. Body weight, FI, and FE changes were also evaluated in response to 5µg KF, centrally administrated.

Results

Chronic administration of KF decreased ∼43% of the density, and ∼30% of the ratio, of activated microglia in the arcuate nucleus. These changes were accompanied by body weight loss, decreased FE, reduced fasting blood glucose, and a tendency to improve insulin sensitivity. Finally, acute central administration of KF reproduced the effects on EB triggered by peripheral administration.

Conclusion

These findings suggest that KF might fight obesity by regulating central processes related to EB regulation and hypothalamic inflammation.

GRAPHICAL ABSTRACT

KEYWORDS:

• Kaempferol
• obesity
• energy balance
• hypothalamic inflammation
• microglia

Acknowledgements

The authors are grateful to Ruby Guzman and Alejandro López Jaimes (Language Coordinator of the Higher Technological Institute of Tacámbaro) for the language review of this manuscript.

Disclosure statement

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

Data availability statement

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

Additional information

Funding

This study was funded in part by the ‘Tecnológico Nacional de México’ through the Program ‘Apoyos a la investigación científica y tecnológica de instituciones académicas y sector público’ [44401-01/2019] – Mexico; the Mexican ‘Consejo Nacional de Ciencia y Tecnología’ (CONACYT) [CB-2014243419], ‘Fundação de Amparo à Ciência e Tecnologia de Pernambuco’ (FACEPE) – Brazil; ‘Coordenação de Aperfeiçoamento de Pessoal de Nível Superior’ (CAPES) [Financial code - 001] – Brazil; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [#429610/2018-1] – Brazil. Diego Bulcão Visco and Luis Miguel Saavedra were funded by PhD fellowships from the Brazilian FACEPE and the Mexican ‘Consejo Nacional de Ciencia y Tecnología’ (CONACYT), respectively.

Notes on contributors

Pedro A. Romero-Juárez

P. A. Romero-Juárez is a M.Sc. student at ‘Master’s Program in Biomedical Sciences’, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Mexico. His work is developed in the field of neuroscience, nutrition, and phenotypic plasticity, focusing on the study of the pathogenesis and therapy of metabolic disorders.

Diego Bulcão Visco

D. B. Visco is a PhD student at ‘Postgraduate Program in Nutrition’, Federal University of Pernambuco, Recife, Brazil. His work is developed in the field of neuroscience, nutrition, cerebral palsy, and phenotypic plasticity.

Raul Manhães-de-Castro

R. Manhaes-de-Castro is an Emeritus Professor at Federal University of Pernambuco, Recife, Brazil. His work is developed in the field of neuroscience, nutrition and phenotypic plasticity.

Mercedes V. Urquiza-Martínez

M. V. Urquiza-Martínez is a PhD carrying out her work in the field of neuroscience, nutrition, and phenotypic plasticity, focusing on the study of the pathogenesis and nutritional therapy of metabolic disorders.

Luis Miguel Saavedra

L. M. Saavedra is a PhD student at Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Mexico. His work is developed in the field of neuroscience, nutrition, and phenotypic plasticity, focusing on the study of the early stress exposure and its long-term consequences.

Mari C. González-Vargas

M. C. González-Vargas is a technician at Higher Technological Institute of Tacambaro, Tacambaro, Mexico, conducting behavioral studies and diet modeling.

Rosalio Mercado-Camargo

R. Mercado-Camargo is a Professor at Faculty of Chemistry- Pharmacobiology, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Mexico. He carries out his work in the field of neuroscience, nutrition, and phenotypic plasticity, focusing on the study of the pathogenesis and therapy of metabolic disorders.

Jailane de Souza Aquino

J. de Souza Aquino is a Professor at Department of Nutrition, Federal University of Paraiba. Her work is carried out in the field of nutrition, functional foods, and phenotypic plasticity.

Ana E. Toscano

A. E. Toscano is a Professor at Department of Nursing, CAV, Federal University of Pernambuco. Her work is carried out in the field of neuroscience, nutrition, cerebral palsy, and phenotypic plasticity.

Luz Torner

L. Torner is a Senior Researcher at Biomedical Research Center of Michoacan, Social Security Mexican Institute, Morelia, Mexico. She carries out her studies in the field of neuroscience, nutrition, and phenotypic plasticity, focusing on the study of the early stress exposure and its long-term consequences.

Omar Guzmán-Quevedo

O. Guzmán-Quevedo is a Professor at Higher Technological Institute of Tacambaro, Tacambaro, Mexico. He carries out his work in the field of neuroscience, nutrition, and phenotypic plasticity, focusing on the study of the pathogenesis and nutritional therapy of metabolic disorders.