title: Gamma-linolenic acid, Dihommo-gamma linolenic, Eicosanoids and Inflammatory Processes.
abstract: Gamma-linolenic acid (GLA, 18:3n-6) is an omega-6 (n-6), 18 carbon (18C-) polyunsaturated fatty acid (PUFA) found in human milk and several botanical seed oils and is typically consumed as part of a dietary supplement. While there have been numerous in vitro and in vivo animal models which illustrate that GLA-supplemented diets attenuate inflammatory responses, clinical studies utilizing GLA or GLA in combination with omega-3 (n-3) PUFAs have been much less conclusive. A central premise of this review is that there are critical metabolic and genetic factors that affect the conversion of GLA to dihommo-gamma linolenic acid (DGLA, 20:3n-6) and arachidonic acid (AA, 20:4n-6), which consequently affects the balance of DGLA- and AA- derived metabolites. As a result, these factors impact the clinical effectiveness of GLA or GLA/(n-3) PUFA supplementations in treating inflammatory conditions. Specifically, these factors include: 1) the capacity for different human cells and tissues to convert GLA to DGLA and AA and to metabolize DGLA and AA to bioactive metabolites; 2) the opposing effects of DGLA and AA metabolites on inflammatory processes and diseases; and 3) the impact of genetic variations within the fatty acid desaturase (FADS) gene cluster, in particular, on AA/DGLA ratios and bioactive metabolites. We postulate that these factors influence the heterogeneity of results observed in GLA supplement-based clinical trials and suggest that "one-size fits all" approaches utilizing PUFA-based supplements may no longer be appropriate for the prevention and treatment of complex human diseases.
authors.affiliation: Department of Biochemistry; Wake Forest School of Medicine, One Medical Center Blvd, Winston-Salem, NC 27157, USA. Electronic address: ssergean@wakehealth.edu.
authors.forename: Susan
authors.initials: S
authors.lastname: Sergeant
authors.affiliation: Department of Biomedical Engineering; Wake Forest School of Medicine, One Medical Center Blvd, Winston-Salem, NC 27157, USA. Electronic address: erahbar@wakehealth.edu.
authors.forename: Elaheh
authors.initials: E
authors.lastname: Rahbar
authors.affiliation: Department of Physiology/Pharmacology, Wake Forest School of Medicine, One Medical Center Blvd, Winston-Salem, NC 27157, USA. Electronic address: schilton@wakehealth.edu.
authors.forename: Floyd H
authors.initials: FH
authors.lastname: Chilton
mesh_terms: D000818:Animals; D019587:Dietary Supplements; D015777:Eicosanoids / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family / Q000235:genetics; D017965:gamma-Linolenic Acid / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D015777:Eicosanoids; D017965:gamma-Linolenic Acid
keywords: Arachidonic acid; Dihommo gamma-linolenic acid; Eicosanoid; Gamma-linolenic acid; Inflammation