Resolvin E1 derived from eicosapentaenoic acid prevents hyperinsulinemia and hyperglycemia in a host genetic manner

Pal, Anandita; Al-Shaer, Abrar E.; Guesdon, William; Torres, Marı́a José; Armstrong, Michael; Quinn, Kevin; Davis, Traci; Reisdorph, Nichole; Neufer, P. Darrell; Spangenburg, Espen E.; Carroll, Ian M.; Bazinet, Richard P.; Halade, Ganesh V.; Clària, Joan; Shaikh, Saame Raza

doi:10.1096/fj.202000830r

Cited by 45 publications

(35 citation statements)

References 68 publications

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“…Supporting experiments with gain and loss of function approaches in animal models are also required to establish that SPM deficiencies in obesity exacerbate the response to the infection. It is also important to consider the host genetic profile ( 34 ), which could be a major consideration in developing dietary or pharmacological approaches to overcoming SPM deficiencies and improving outcomes to SARS-CoV-2 for the obese.…”

Section: Discussionmentioning

confidence: 99%

“…To exemplify, obese mice compared to lean controls display a rapid reduction in DHA-derived SPM precursors and SPMs in white adipose tissue within 4 days of consuming a high fat diet ( 37 ). Others have also reported a reduction of not only DHA-derived SPMs but also metabolites from the EPA pathway upon long term consumption of obesogenic diets in white adipose tissue and liver, which are central in driving complications of obesity ( 30 , 32 , 34 , 42 ). As described below, these deficiencies can be overcome through dietary administration of EPA- or DHA-enriched marine oils.…”

Section: Obesity Promotes a Signature Of Spm Deficiencymentioning

confidence: 99%

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Obesity-Driven Deficiencies of Specialized Pro-resolving Mediators May Drive Adverse Outcomes During SARS-CoV-2 Infection

et al. 2020

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Obesity is a major independent risk factor for increased morbidity and mortality upon infection with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), which is responsible for the current coronavirus disease pandemic (COVID-19). Therefore, there is a critical need to identify underlying metabolic factors associated with obesity that could be contributing toward increased susceptibility to SARS-CoV-2 in this vulnerable population. Here, we focus on the critical role of potent endogenous lipid metabolites known as specialized pro-resolving mediators (SPMs) that are synthesized from polyunsaturated fatty acids. SPMs are generated during the transition of inflammation to resolution and have a vital role in directing damaged tissues to homeostasis; furthermore, SPMs display anti-viral activity in the context of influenza infection without being immunosuppressive. We cover evidence from rodent and human studies to show that obesity, and its co-morbidities, induce a signature of SPM deficiency across immunometabolic tissues. We further discuss how the effects of obesity upon SARS-CoV-2 infection are likely exacerbated with environmental exposures that promote chronic pulmonary inflammation and augment SPM deficits. Finally, we highlight potential approaches to overcome the loss of SPMs using dietary and pharmacological interventions. Collectively, this mini-review underscores the need for mechanistic studies on how SPM deficiencies driven by obesity and environmental exposures may exacerbate the response to SARS-CoV-2.

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Section: Discussionmentioning

confidence: 99%

Section: Obesity Promotes a Signature Of Spm Deficiencymentioning

confidence: 99%

Obesity-Driven Deficiencies of Specialized Pro-resolving Mediators May Drive Adverse Outcomes During SARS-CoV-2 Infection

et al. 2020

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“…Furthermore, application of Cox-2 inhibitors increases cardiovascular risks. On the other hand, therapies targeting TNF signaling raise the risks for infections and lymphoma and non-melanoma skin cancer [ 9 , 20 , 94 , 95 , 96 ]. In addition, prostaglandins PGE2 and PGD2 are crucial for the initiation of resolution as described above and the inhibition of their biosynthesis may thus be counterproductive [ 25 ].…”

Section: Spms: Potential New Treatment Options For Pcosmentioning

confidence: 99%

Chronic Inflammation in PCOS: The Potential Benefits of Specialized Pro-Resolving Lipid Mediators (SPMs) in the Improvement of the Resolutive Response

Regidor¹,

Mueller²,

Sailer³

et al. 2020

IJMS

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PCOS as the most common endocrine disorder of women in their reproductive age affects between 5–15% of the female population. Apart from its cardinal symptoms, like irregular and anovulatory cycles, hyperandrogenemia and a typical ultrasound feature of the ovary, obesity, and insulin resistance are often associated with the disease. Furthermore, PCOS represents a status of chronic inflammation with permanently elevated levels of inflammatory markers including IL-6 and IL-18, TNF-α, and CRP. Inflammation, as discovered only recently, consists of two processes occurring concomitantly: active initiation, involving “classical” mediators including prostaglandins and leukotrienes, and active resolution processes based on the action of so-called specialized pro-resolving mediators (SPMs). These novel lipid mediator molecules derive from the essential ω3-poly-unsaturated fatty acids (PUFAs) DHA and EPA and are synthesized via specific intermediates. The role and benefits of SPMs in chronic inflammatory diseases like obesity, atherosclerosis, and Diabetes mellitus has become a subject of intense research during the last years and since PCOS features several of these pathologies, this review aims at summarizing potential roles of SPMs in this disease and their putative use as novel therapeutics.

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“…In. this context, recent studies demonstrate that the ability of the EPA-derived SPM RvE1 to reverse hyperinsulinemia and hyperglycemia in obese outbred mice was linked with SNPs identified in its cognate receptor ERV1/ChemR23 [ 49 ]. Therefore, future studies we will need to evaluate the efficiency of conversion to bioactive mediators for these supplements in target disease population(s) in order to evaluate their potential therapeutic utility.…”

Section: Discussionmentioning

confidence: 99%

Protective activities of distinct omega-3 enriched oils are linked to their ability to upregulate specialized pro-resolving mediators

et al. 2020

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Clinical studies using a range of omega-3 supplements have yielded conflicting results on their efficacy to control inflammation. Omega-3 fatty acids are substrate for the formation of potent immune-protective mediators, termed as specialized pro-resolving mediators (SPM). Herein, we investigated whether observed differences in the potencies of distinct omega-3 supplements were linked with their ability to upregulate SPM formation. Using lipid mediator profiling we found that four commercially available supplements conferred a unique SPM signature profile to human macrophages, with the overall increases in SPM concentrations being different between the four supplements. These increases in SPM concentrations were linked with an upregulation of macrophage phagocytosis and a decreased uptake of oxidized low-density lipoproteins. Pharmacological inhibition of two key SPM biosynthetic enzymes 5-Lipoxygenase or 15-Lipoxygenase reversed the macrophage-directed actions of each of the omega-3 supplements. Furthermore, administration of the two supplements that most potently upregulated macrophage SPM formation and reprogrammed their responses in vitro, to APOE-/- mice fed a western diet, increased plasma SPM concentrations and reduced vascular inflammation. Together these findings support the utility of SPM as potential prognostic markers in determining the utility of a given supplement to regulate macrophage responses and inflammation.

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Resolvin E1 derived from eicosapentaenoic acid prevents hyperinsulinemia and hyperglycemia in a host genetic manner

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 45 publications

References 68 publications

Obesity-Driven Deficiencies of Specialized Pro-resolving Mediators May Drive Adverse Outcomes During SARS-CoV-2 Infection

Obesity-Driven Deficiencies of Specialized Pro-resolving Mediators May Drive Adverse Outcomes During SARS-CoV-2 Infection

Chronic Inflammation in PCOS: The Potential Benefits of Specialized Pro-Resolving Lipid Mediators (SPMs) in the Improvement of the Resolutive Response

Protective activities of distinct omega-3 enriched oils are linked to their ability to upregulate specialized pro-resolving mediators

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