Odd Chain Fatty Acids; New Insights of the Relationship Between the Gut Microbiota, Dietary Intake, Biosynthesis and Glucose Intolerance

Benjamin Jenkins ,James A West,Stéphane Hazebrouck,Pin-Ho Pan,Ronald M Krauss,Kévin Seyssel ,Sally Chiu,Maud Alligier,Shih‐Yi Lin ,Samuel T King ,Martin J J Ronis ,Paul P Van Veldhoven,Walter Vetter,Kalervo Hiltunen,Renata Štěpánková ,Elizabeth Stanley,Evelyn De Schryver,Guillaume Kraft,Alan D Cherrington ,Mary Courtney Moore ,Martine Laville,Chun‐Jung Chen ,Keith Summerhill,Julian L Griffin,Zsuzsanna Ament,Kaija J Autio,Albert Koulman

doi:10.1038/srep44845

Abstract

Recent findings have shown an inverse association between circulating C15:0/C17:0 fatty acids with disease risk, therefore, their origin needs to be determined to understanding their role in these pathologies. Through combinations of both animal and human intervention studies, we comprehensively investigated all possible contributions of these fatty acids from the gut-microbiota, the diet, and novel endogenous biosynthesis. Investigations included an intestinal germ-free study and a C15:0/C17:0 diet dose response study. Endogenous production was assessed through: a stearic acid infusion, phytol supplementation, and a Hacl1−/− mouse model. Two human dietary intervention studies were used to translate the results. Finally, a study comparing baseline C15:0/C17:0 with the prognosis of glucose intolerance. We found that circulating C15:0/C17:0 levels were not influenced by the gut-microbiota. The dose response study showed C15:0 had a linear response, however C17:0 was not directly correlated. The phytol supplementation only decreased C17:0. Stearic acid infusion only increased C17:0. Hacl1−/− only decreased C17:0. The glucose intolerance study showed only C17:0 correlated with prognosis. To summarise, circulating C15:0 and C17:0 are independently derived; C15:0 correlates directly with dietary intake, while C17:0 is substantially biosynthesized, therefore, they are not homologous in the aetiology of metabolic disease. Our findings emphasize the importance of the biosynthesis of C17:0 and recognizing its link with metabolic disease.

Highlights

Metabolomics and Lipidomics Laboratory, Level 4, Laboratory Block, Cambridge University Hospitals, University of Cambridge, Cambridge, UK
Recent findings have shown a negative association between circulating odd chain fatty acids (OC-FAs); pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0), with metabolic disease risk[1,2]
Any variation in circulating C15:0 and C17:0 has been attributed to variations in ruminant fat intake with no consideration of biosynthesis. We investigated how these OC-FAs correlate with the development of glucose intolerance during a controlled high fat diet in a canine model; the canine model was selected due to the sample volume requirements of the study and it has been previously shown that dogs are a suitably comparable model to human glucose intolerance pathology

Summary

Introduction

Metabolomics and Lipidomics Laboratory, Level 4, Laboratory Block, Cambridge University Hospitals, University of Cambridge, Cambridge, UK. To summarise, circulating C15:0 and C17:0 are independently derived; C15:0 correlates directly with dietary intake, while C17:0 is substantially biosynthesized, they are not homologous in the aetiology of metabolic disease. The origin of C15:0 and C17:0 has long been attributed to the diet[3,4], from ruminant fat as the main contributor in a typical Western diet. This has been explained by the fact that these two OC-FAs are produced by the rumen microbiome[5] and incorporated into the fat deposits of the host animal destined for human consumption. We used a the combination of both different animal and human studies we are able for the first time to comprehensively study the many aspects of circulating OC-FAs

Methods

Results

Conclusion