Molecular Neurobiology

, Volume 55, Issue 9, pp 7285–7296 | Cite as

Buttermilk and Krill Oil Phospholipids Improve Hippocampal Insulin Resistance and Synaptic Signaling in Aged Rats

  • Joao Tomé-Carneiro
  • M. Carmen Crespo
  • Emma Burgos-Ramos
  • Cristina Tomas-Zapico
  • Alba García-Serrano
  • Pilar Castro-Gómez
  • Cesar Venero
  • Inmaculada Pereda-Pérez
  • Shishir Baliyan
  • Azucena Valencia
  • Javier Fontecha
  • Alberto DávalosEmail author
  • Francesco Visioli


Impaired glucose metabolism and mitochondrial decay greatly increase with age, when cognitive decline becomes rampant. No pharmacological or dietary intervention has proven effective, but proper diet and lifestyle do postpone the onset of neurodegeneration and some nutrients are being investigated. We studied insulin signaling, mitochondrial activity and biogenesis, and synaptic signaling in the hippocampus and cortex following dietary supplementation with bioactive phospholipid concentrates of krill oil (KOC), buttermilk fat globule membranes (BMFC), and a combination of both in aged rats. After 3 months of supplementation, although all groups of animals showed clear signs of peripheral insulin resistance, the combination of KOC and BMFC was able to improve peripheral insulin sensitivity. We also explored brain energy balance. Interestingly, the hippocampus of supplemented rats—mainly when supplemented with BMFC or the combination of KOC and BMFC—showed an increase in intracellular adenosine triphosphate (ATP) levels, whereas no difference was observed in the cerebral cortex. Moreover, we found a significant increase of brain-derived neurotrophic factor (BDNF) in the hippocampus of BMFC+KO animals. In summary, dietary supplementation with KOC and/or BMFC improves peripheral and central insulin resistance, suggesting that their administration could delay the onset of these phenomena. Moreover, n-3 fatty acids (FAs) ingested as phospholipids increase BDNF levels favoring an improvement in energy state within neurons and facilitating both mitochondrial and protein synthesis, which are necessary for synaptic plasticity. Thus, dietary supplementation with n-3 FAs could protect local protein synthesis and energy balance within dendrites, favoring neuronal health and delaying cognitive decline associated to age-related disrepair.


Insulin Hippocampus Phospholipids Buttermilk Krill oil 



Alzheimer’s disease


Protein kinase B


AMP-activated protein kinase


Chaperone α-synuclein


Adenosine triphosphate


Brain-derived neurotrophic factor


Buttermilk fat globule concentrate


Cognitive deficiency


Docosahexaenoic acid


Eicosapentaenoic acid


Fatty acids


Glucose transporter type 4


Homeostasis model assessment of insulin resistance index


Insulin receptor-beta subunit


Insulin receptor substrate


Krill oil concentrate


Milk fat globule membrane


Mammalian target of rapamycin


Polyunsaturated fatty acid










Pressurized liquid extraction




Proliferator-activated receptor γ coactivator 1-α




Sirtuin 1


Syntaxin 1A


Synapsin I


Synaptotagmin 1




Synaptobrevin 2



Buttermilk powder was a kind gift of Reny Picot (Oviedo, Spain), and Antarctic krill oil from Euphausia superba was kindly donated by AKO3 (Aker Biomarine Antarctic AS, Oslo, Norway).

Author Contributions

JF, CV, and FV designed the study. JTC, MCC, EBR, IPP, SB AGS, PCG, and AV performed experiments. MCC, JTC, EBR, CTZ, AD, and FV wrote the manuscript. All authors approved the submission of the final version of the manuscript.

Funding Information

This study was supported in part by grants from the Spanish Ministerio de Economía y Competitividad (AGL2014-56464-R1 and AGL2014-54565-R2); by the Comunidad de Madrid through the “Programa de actividades en tecnologias” (ALIBIRD-CM S2013/ABI-2728); and by the Castilla-La Mancha University through the “Programa de ayuda I+D a grupos emergentes” (GI20173998) to EBR. AD lab is supported in part by the Spanish Agencia Estatal de Investigación and European Feder Funds (AGL2016-78922-R) and Fundación Ramón Areces (Madrid, Spain).

Compliance with Ethical Standard

Animal experiments were approved by the Animal Experimentation Committee of the National Distance Education University (UNED, Spain).

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2018_934_MOESM1_ESM.docx (20 kb)
ESM 1 (DOCX 20 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Joao Tomé-Carneiro
    • 1
  • M. Carmen Crespo
    • 1
  • Emma Burgos-Ramos
    • 2
  • Cristina Tomas-Zapico
    • 3
    • 4
  • Alba García-Serrano
    • 5
  • Pilar Castro-Gómez
    • 5
  • Cesar Venero
    • 6
  • Inmaculada Pereda-Pérez
    • 6
    • 7
  • Shishir Baliyan
    • 6
  • Azucena Valencia
    • 6
  • Javier Fontecha
    • 5
  • Alberto Dávalos
    • 8
    Email author
  • Francesco Visioli
    • 1
    • 9
  1. 1.Laboratory of Functional FoodsMadrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSICMadridSpain
  2. 2.Área de BioquímicaUniversidad de Castilla-La-ManchaToledoSpain
  3. 3.Department of Functional Biology (Physiology)University of OviedoOviedoSpain
  4. 4.Universidad Autónoma de ChileSantiagoChile
  5. 5.Institute of Food Science Research, Spanish National Research Council (CIAL, CSIC-UAM), Bioactivity and Food Analysis Department, Food Lipid Biomarkers and HealthCampus of Autónoma University of MadridMadridSpain
  6. 6.Department of Psychobiology, Faculty of PsychologyUNEDMadridSpain
  7. 7.Faculty of Biosanitary SciencesFrancisco de Vitoria UniversityMadridSpain
  8. 8.Laboratory of Epigenetics of Lipid MetabolismMadrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSICMadridSpain
  9. 9.Department of Molecular MedicineUniversity of PadovaPadovaItaly

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