Coordination of GPR40 and Ketogenesis Signaling by Medium Chain Fatty Acids Regulates Beta Cell Function

Pujol, Julien Benjamin; Christinat, Nicolas; Ratinaud, Yann; Savoia, Claudia; Mitchell, Siobhan E.; Dioum, El Hadji M

doi:10.3390/nu10040473

Submit to this Journal Review for this Journal Edit a Special Issue

Article Menu

...

Open AccessArticle

Coordination of GPR40 and Ketogenesis Signaling by Medium Chain Fatty Acids Regulates Beta Cell Function

Julien Benjamin Pujol

¹,

²,

³,

¹,

⁴ and

^1,*

Islet Function, Nestlé Institute of Health Sciences (NIHS), EPFL Innovation Park, 1015 Lausanne, Switzerland

Lipidomics, Nestlé Institute of Health Sciences (NIHS), EPFL Innovation Park, 1015 Lausanne, Switzerland

Natural Bioactives Screening, Nestlé Institute of Health Sciences (NIHS), EPFL Innovation Park, 1015 Lausanne, Switzerland

⁴

Brain Health, Nestlé Institute of Health Sciences (NIHS), EPFL Innovation Park, 1015 Lausanne, Switzerland

Author to whom correspondence should be addressed.

Nutrients 2018, 10(4), 473; https://doi.org/10.3390/nu10040473

Received: 29 January 2018 / Revised: 26 March 2018 / Accepted: 10 April 2018 / Published: 12 April 2018

View Full-Text Download PDF

Browse Figures

Citation Export

Abstract

Diabetes prevalence increases with age, and β-cell dysfunction contributes to the incidence of the disease. Dietary lipids have been recognized as contributory factors in the development and progression of the disease. Unlike long chain triglycerides, medium chain triglycerides (MCT) increase fat burning in animal and human subjects as well as serum C-peptide in type 2 diabetes patients. We evaluated the beneficial effects of MCT on β-cells in vivo and in vitro. MCT improved glycemia in aged rats via β-cell function assessed by measuring insulin secretion and content. In β-cells, medium chain fatty acid (MCFA)-C10 activated fatty acid receptor 1 FFAR1/GPR40, while MCFA-C8 induced mitochondrial ketogenesis and the C8:C10 mixture improved β cell function. We showed that GPR40 signaling positively impacts ketone body production in β-cells, and chronic treatment with β-hydroxybutyrate (BHB) improves β-cell function. We also showed that BHB and MCFA help β-cells recover from lipotoxic stress by improving mitochondrial function and increasing the expression of genes involved in β-cell function and insulin biogenesis, such as Glut2, MafA, and NeuroD1 in primary human islets. MCFA offers a therapeutic advantage in the preservation of β-cell function as part of a preventative strategy against diabetes in at risk populations. View Full-Text

Keywords: insulin secretion; mitochondria; medium chain fatty acid; lipotoxicity; ketogenesis; BHB; GPR40

▼ Show Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Supplementary Material

Supplementary File 1:
PDF-Document (PDF, 321 KiB)

Share and Cite

MDPI and ACS Style

Pujol, J.B.; Christinat, N.; Ratinaud, Y.; Savoia, C.; Mitchell, S.E.; Dioum, E.H.M. Coordination of GPR40 and Ketogenesis Signaling by Medium Chain Fatty Acids Regulates Beta Cell Function. Nutrients 2018, 10, 473. https://doi.org/10.3390/nu10040473

AMA Style

Pujol JB, Christinat N, Ratinaud Y, Savoia C, Mitchell SE, Dioum EHM. Coordination of GPR40 and Ketogenesis Signaling by Medium Chain Fatty Acids Regulates Beta Cell Function. Nutrients. 2018; 10(4):473. https://doi.org/10.3390/nu10040473

Chicago/Turabian Style

Pujol, Julien B., Nicolas Christinat, Yann Ratinaud, Claudia Savoia, Siobhan E. Mitchell, and El H.M. Dioum. 2018. "Coordination of GPR40 and Ketogenesis Signaling by Medium Chain Fatty Acids Regulates Beta Cell Function" Nutrients 10, no. 4: 473. https://doi.org/10.3390/nu10040473

Find Other Styles

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Abstract views Pdf views Html views

Article Menu

Coordination of GPR40 and Ketogenesis Signaling by Medium Chain Fatty Acids Regulates Beta Cell Function

Abstract

Supplementary Material

Share and Cite

Article Metrics

Article Access Statistics

Article Access Map by Country/Region

Further Information

Guidelines

MDPI Initiatives

Follow MDPI