Odd Chain Fatty Acids; New Insights of the Relationship Between the Gut Microbiota, Dietary Intake, Biosynthesis and Glucose Intolerance.
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.
Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, CB1 9NL. Affiliated with the University of Cambridge, United Kingdom.
Benjamin J
BJ
Jenkins
Lyon University, INSERM U1060, CarMeN Laboratory and CENS, Claude Bernard University, CRNH Rhône-Alpes, Centre Hospitalier Lyon-Sud, 69310, Pierre-Bénite, France.
Kevin
K
Seyssel
Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, United States of America.
Sally
S
Chiu
Department of Pediatrics, Tungs' Taichung MetroHarbor Hospital, Taichung 435, Taiwan.
Pin-Ho
PH
Pan
Division of Endocrinology and Metabolism/Center for Geriatrics and Gerontology, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Boulevard, Taichung 407, Taiwan.
Shih-Yi
SY
Lin
Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, CB1 9NL. Affiliated with the University of Cambridge, United Kingdom.
Elizabeth
E
Stanley
Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, CB1 9NL. Affiliated with the University of Cambridge, United Kingdom.
Zsuzsanna
Z
Ament
Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, CB1 9NL. Affiliated with the University of Cambridge, United Kingdom.
James A
JA
West
Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, CB1 9NL. Affiliated with the University of Cambridge, United Kingdom.
Keith
K
Summerhill
Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, CB1 9NL. Affiliated with the University of Cambridge, United Kingdom.
Julian L
JL
Griffin
University of Hohenheim, Institute of Food Chemistry, Garbenstrasse 28, D-70599 Stuttgart, Germany.
Walter
W
Vetter
Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, P.O. Box 5400, FI-90014, Finland.
Kaija J
KJ
Autio
Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, P.O. Box 5400, FI-90014, Finland.
Kalervo
K
Hiltunen
UMR CEA-INRA Service de Pharmacologie et d'Immunoanalyse, Laboratoire d'Immuno-Allergie Alimentaire, Université Paris-Saclay, F-91991 Gif-sur-Yvette, France.
Stéphane
S
Hazebrouck
Laboratory of Gnotobiology, Institute of Microbiology, Czech Academy of Science, Novy Hradek, 549 22, Prague, Czech Republic.
Renata
R
Stepankova
Department of Medical Research, Taichung Veterans General Hospital, No. 1650, Sec.4, Taiwan Boulevard, Taichung 407, Taiwan.
Chun-Jung
CJ
Chen
Lyon University, INSERM U1060, CarMeN Laboratory and CENS, Claude Bernard University, CRNH Rhône-Alpes, Centre Hospitalier Lyon-Sud, 69310, Pierre-Bénite, France.
Maud
M
Alligier
Lyon University, INSERM U1060, CarMeN Laboratory and CENS, Claude Bernard University, CRNH Rhône-Alpes, Centre Hospitalier Lyon-Sud, 69310, Pierre-Bénite, France.
Martine
M
Laville
702 Light Hall, Dept. of Molecular Physiology &Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615, United States of America.
Mary
M
Moore
702 Light Hall, Dept. of Molecular Physiology &Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615, United States of America.
Guillaume
G
Kraft
702 Light Hall, Dept. of Molecular Physiology &Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615, United States of America.
Alan
A
Cherrington
Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, United States of America.
Sarah
S
King
Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, United States of America.
Ronald M
RM
Krauss
Laboratory of Lipid Biochemistry and Protein Interactions (LIPIT), Campus Gasthuisberg - KU Leuven, Herestraat Box 601, B-3000 Leuven, Belgium.
Evelyn
E
de Schryver
Laboratory of Lipid Biochemistry and Protein Interactions (LIPIT), Campus Gasthuisberg - KU Leuven, Herestraat Box 601, B-3000 Leuven, Belgium.
Paul P
PP
Van Veldhoven
College of Medicine, Department of Pharmacology &Experimental Therapeutics, Louisiana State University Health Sciences Centre 1901 Perdido Str., New Orleans, United States of America.
Martin
M
Ronis
Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, CB1 9NL. Affiliated with the University of Cambridge, United Kingdom.|NIHR BRC Core Metabolomics and Lipidomics Laboratory, Level 4, Laboratory Block, Cambridge University Hospitals, University of Cambridge, Cambridge, UK.
Albert
A
Koulman
D000818:Animals; D053898:Biosynthetic Pathways; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism; D000073417:Dietary Sugars / Q000008:administration & dosage / Q000378:metabolism*; D019587:Dietary Supplements; D005227:Fatty Acids / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome; D018149:Glucose Intolerance; D005951:Glucose Tolerance Test; D006801:Humans; D051379:Mice; D051381:Rats
D004041:Dietary Fats; D000073417:Dietary Sugars; D005227:Fatty Acids