Δ-5 Fatty Acid Desaturase
            <i>FADS1</i>
            Impacts Metabolic Disease by Balancing Proinflammatory and Proresolving Lipid Mediators

Gromovsky, Anthony D.; Schugar, Rebecca C.; Brown, Amanda; Helsley, Robert N; Burrows, Amy; Ferguson, Daniel; Zhang, Renliang; Sansbury, Brian E.; Lee, Richard G.; Morton, Richard E.; Allende, Daniela S.; Parks, John S.; Spite, Matthew; Brown, J. Howard

doi:10.1161/atvbaha.117.309660

Cited by 92 publications

(88 citation statements)

References 49 publications

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“…Thus, low-grade systemic inflammatory conditions such as obesity, type 2 diabetes mellitus, hypertension, coronary heart disease, non-alcoholic fatty liver disease (NAFLD), Alzheimer’s disease, depression, schizophrenia, and ageing could be ascribed to decreased formation of anti-inflammatory bioactive lipids such as LXA4, resolvins, protectins and maresins that, in turn, could be due to decreased formation of AA, EPA and DHA from EFAs due to decreased activity of desaturases. In this context, it is interesting to note that in majority of these conditions, the activities of desaturases are altered, plasma and tissue content AA is low compared to that of EPA and DHA, plasma pro-inflammatory PGs and LTs are increased and anti-inflammatory LXA4, resolvins, and protectins are decreased [15] , [23] , [42] , [43] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] implying that the metabolism of EFAs are defective and of all, AA seems to be more crucial role in these diseases. It is important to note that in addition to alterations in the metabolism of AA, there could occur changes in the metabolism of EPA and DHA and their products.…”

Section: Aa Metabolismmentioning

confidence: 99%

Ageing: Is there a role for arachidonic acid and other bioactive lipids? A review

Das¹

2018

Journal of Advanced Research

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Section: Aa Metabolismmentioning

confidence: 99%

Ageing: Is there a role for arachidonic acid and other bioactive lipids? A review

Das¹

2018

Journal of Advanced Research

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“…Network illustration of the enzymes, intermediates, and precursors of the SPM superfamily's biosynthesis from omega-3 PUFA. Deficiencies in the fatty acid desaturase (Fads) gene cluster reduce SPM production(194). Stereochemistry of each major SPM is established; for detailed mechanisms in biosynthesis and complete SPM nomenclature of each endogenous molecule, see refs.…”

mentioning

confidence: 99%

Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators

Serhan¹,

Levy

2018

Journal of Clinical Investigation

961

976

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Countless times each day, the acute inflammatory response protects us from invading microbes, injuries, and insults from within, as in surgery-induced tissue injury. These challenges go unnoticed because they are self-limited and naturally resolve without progressing to chronic inflammation. Peripheral blood markers of inflammation are present in many common diseases, including inflammatory bowel disease, cardiovascular disease, neurodegenerative disease, and cancer. While acute inflammation is protective, excessive swarming of neutrophils amplifies collateral tissue damage and inflammation. Hence, understanding the mechanisms that control the resolution of acute inflammation provides insight into preventing and treating inflammatory diseases in multiple organs. This Review focuses on the resolution phase of inflammation with identification of specialized pro-resolving mediators (SPMs) that involve three separate biosynthetic and potent mediator families, which are defined using the first quantitative resolution indices to score this vital process. These are the resolvins, protectins, and maresins: bioactive metabolomes that each stimulate self-limited innate responses, enhance innate microbial killing and clearance, and are organ-protective. We briefly address biosynthesis of SPMs and their activation of endogenous resolution programs as terrain for new therapeutic approaches that are not, by definition, immunosuppressive, but rather new immunoresolvent therapies.

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“…Estimated D5D and D6D activities were reported to be negatively and positively associated with WAT mRNA expression of IL-1β in obese subjects, respectively (53). In LDL receptor-deficient mice under an ALA-rich diet, FADS1 knockdown results in lower plasma arachidonic acid and EPA and derived proresolving lipid mediators, higher plasma IL-1β, and higher macrophage mRNA expression of IL-1β (54). Thus, given the positive association of the IL-1β system and WAT dysfunction with the pathophysiology of T2D (7,55), the association of D5D, but not D6D, activity, with reduced plasma IL-1Ra and increased WAT function was anticipated.…”

Section: Discussionmentioning

confidence: 99%

The Association of Polyunsaturated Fatty Acid δ-5-Desaturase Activity with Risk Factors for Type 2 Diabetes Is Dependent on Plasma ApoB-Lipoproteins in Overweight and Obese Adults

Lamantia

Bissonnette

Provost

et al. 2019

The Journal of Nutrition

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Background δ-5 and δ-6 desaturases (D5D and D6D) catalyze the endogenous conversion of n–3 (ω-3) and n–6 (ω-6) polyunsaturated fatty acids (PUFAs). Their activities are negatively and positively associated with type 2 diabetes (T2D), respectively, by unclear mechanisms. Elevated plasma apoB-lipoproteins (measured as plasma apoB), which can be reduced by n–3 PUFA intake, promote T2D risk factors. Objective The aim of this study was to test the hypothesis that the association of D5D and D6D activities with T2D risk factors is dependent on plasma apoB. Methods This is a pooled analysis of 2 populations recruited for 2 different metabolic studies. It is a post hoc analysis of baseline data of these subjects [n = 98; 60% women (postmenopausal); mean ± SD body mass index (in kg/m2): 32.8 ± 4.7; mean ± SD age: 57.6 ± 6.3 y]. Glucose-induced insulin secretion (GIIS) and insulin sensitivity (IS) were measured using Botnia clamps. Plasma clearance of a high-fat meal (600 kcal/m2, 66% fat) and white adipose tissue (WAT) function (storage of 3H-triolein-labeled substrate) were assessed in a subpopulation (n = 47). Desaturase activities were estimated from plasma phospholipid fatty acids. Associations were examined using Pearson and partial correlations. Results While both desaturase activities were positively associated with percentage of eicosapentaenoic acid, only D5D was negatively associated with plasma apoB (r = −0.30, P = 0.003). Association of D5D activity with second-phase GIIS (r = −0.23, P = 0.029), IS (r = 0.33, P = 0.015, in women) and 6-h area-under-the-curve (AUC6h) of plasma chylomicrons (apoB48, r = −0.47, P = 0.020, in women) was independent of age and adiposity, but was eliminated after adjustment for plasma apoB. D6D activity was associated in the opposite direction with GIIS (r = 0.24, P = 0.049), IS (r = −0.36, P = 0.004) and AUC6h chylomicrons (r = 0.52, P = 0.004), independent of plasma apoB. Both desaturases were associated with plasma interleukin-1-receptor antagonist (D5D: r = −0.45, P < 0.001 in women; D6D: r = −0.33, P = 0.007) and WAT function (trend for D5D: r = 0.30, P = 0.05; D6D: r = 0.39, P = 0.027) independent of any adjustment. Conclusions Association of D5D activity with IS, lower GIIS, and plasma chylomicron clearance is dependent on plasma apoB in overweight and obese adults.

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Δ-5 Fatty Acid Desaturase FADS1 Impacts Metabolic Disease by Balancing Proinflammatory and Proresolving Lipid Mediators

Abstract: These results position as an underappreciated regulator of inflammation initiation and resolution, and suggest that endogenously synthesized arachidonic acid and eicosapentaenoic acid are key determinates of inflammatory disease progression and liver X receptor signaling.

Cited by 92 publications

References 49 publications

Ageing: Is there a role for arachidonic acid and other bioactive lipids? A review

Ageing: Is there a role for arachidonic acid and other bioactive lipids? A review

Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators

The Association of Polyunsaturated Fatty Acid δ-5-Desaturase Activity with Risk Factors for Type 2 Diabetes Is Dependent on Plasma ApoB-Lipoproteins in Overweight and Obese Adults

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