Activation of the 12/15 lipoxygenase pathway accompanies metabolic decline in db/db pre-diabetic mice

Dobrian, Anca D.; Huyck, Ryan W.; Glenn, Lindsey; Gottipati, Vijay; Haynes, Bronson A.; Hansson, Göran; Marley, Anna; McPheat, William L.; Nadler, Jerry L.

doi:10.1016/j.prostaglandins.2018.03.003

Cited by 13 publications

(16 citation statements)

References 55 publications

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“…In the db /db model of T2D, both forms of 12/15-LOX are expressed in islets (12-LOX and 15-LOX). The islet 12/15-LOX increase parallels the decline in beta cell mass (Dobrian et al, 2018). Collectively, studies conducted in mouse models of T2D strongly support the causal relationship between 12/15-LOX activity and beta cell dysfunction in T2D.…”

Section: Role Of 12/15-lox In Islet Dysfunction Using Mouse Models Ofmentioning

confidence: 62%

“…Zucker obese rats, a genetically-induced model of obesity and insulin resistance, also exhibit increased expression of 12/15-LOX in isolated white adipocytes compared to lean controls (Chakrabarti et al, 2011). Also, more recent data from our lab showed that both 12/15-LOX and 12-LOX are present in AT and adipocytes from db/db mice, and they undergo expressional increases that coincide with the metabolic decline (Dobrian, et al, 2018).…”

Section: Role Of 12-lox and 12/15-lox In Adipose Tissue In Obesity Anmentioning

confidence: 67%

“…The 12-hydroxy docosahexaenoic acid metabolite, along with protectin D1 and resolvin D1, were identified in AT of obese ob/ob mice (Gonzalez-Periz et al, 2009). Recent data from our laboratory also showed a variety of both pro-and anti-inflammatory lipid mediators in the SVF of db/db mice, which showed a change in abundance as the mice became more glucose intolerant and insulin resistant (Dobrian et al, 2018).…”

Section: Role Of 12-lox and 12/15-lox In Adipose Tissue In Obesity Anmentioning

confidence: 83%

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Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications

Dobrian

Morris

Taylor‐Fishwick

et al. 2019

Pharmacology & Therapeutics

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12-lipoxygenase (12-LOX) is one of several enzyme isoforms responsible for the metabolism of arachidonic acid and other poly-unsaturated fatty acids to both pro-and anti-inflammatory lipid mediators. Mounting evidence has shown that 12-LOX plays a critical role in the modulation of inflammation at multiple checkpoints during diabetes development. Due to this, interventions to limit pro-inflammatory 12-LOX metabolites either by isoform-specific 12-LOX inhibition, or by providing specific fatty acid substrates via dietary intervention, has the potential to significantly

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Section: Role Of 12/15-lox In Islet Dysfunction Using Mouse Models Ofmentioning

confidence: 62%

Section: Role Of 12-lox and 12/15-lox In Adipose Tissue In Obesity Anmentioning

confidence: 67%

Section: Role Of 12-lox and 12/15-lox In Adipose Tissue In Obesity Anmentioning

confidence: 83%

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Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications

Dobrian

Morris

Taylor‐Fishwick

et al. 2019

Pharmacology & Therapeutics

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“…Additionally, 5(S)-HETE, 12(S)-HETE and 15(S)-HETE concentrations increased proportionally to body mass [11,18,35,36]. In obese patients with T2D and in an animal model, 12(S)-HETE was described as an indicator of inflammatory processes in white adipose tissue [37,38].…”

Section: Discussionmentioning

confidence: 95%

5-Lipooxygenase Derivatives as Serum Biomarkers of a Successful Dietary Intervention in Patients with NonAlcoholic Fatty Liver Disease

et al. 2020

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Background: It was previously shown that a bodyweight reduction among patients with nonalcoholic fatty liver (NAFLD) was connected to the lower concentration of arachidonic and linoleic acid derivatives in their blood. We hypothesized that the concentration of these lipids was correlated with the extent of their body mass reduction and, thus, liver steatosis. Methods: We analyzed 68 individuals who completed the dietary intervention. Patients were divided into two groups depending on their body mass reduction (more or less than 7%). Before and after the dietary intervention, all patients had the following measurements recorded: body mass, waist circumference, stage of steatosis, fatty liver index, liver enzymes, lipid parameters, insulin and glucose. Concentrations of lipoxins A4 (LTX A4), hydroxyeicosatetraenoic fatty acids (5(S)-HETE, 12(S)-HETE and 16(S)-HETE), hydroxyoctadecaenoic acids (9(S)-HODE and 13(S)-HODE) and 5-oxo-eicosatetraenoic acid (5-oxo-ETE) were measured in serum samples collected before and after the dietetic intervention using high-performance liquid chromatography (HPLC). Results: Patients who reduced their body mass by more than 7% revealed a significant improvement in their steatosis stage, waist circumference, fatty liver index, triglycerides and cholesterol. Conclusion: A reduction in body mass by more than 7% but not by less than 7% revealed a significant improvement in steatosis stage; waist circumference; fatty liver index; and levels of triglycerides, cholesterol, 5-oxo-ETE and LTXA-4.

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“…Recently, it was also reported that cell specific deletion of 12/15-LOX in islets results in improved insulin secretion and protection from any abnormalities in blood glucose levels due to HFD feeding (243). In addition, a substantial increase in 12/15-LOX levels were reported in pancreatic islets of 10-week old db/db prediabetic mice and the increase in 12/15-LOX levels goes in tandem with a decrease in islet number (244).…”

Section: /15-lipoxygenase and Diabetesmentioning

confidence: 99%

Emerging role of 12/15-Lipoxygenase (ALOX15) in human pathologies

Singh

Rao

2019

Progress in Lipid Research

223

163

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12/15-lipoxygenase (12/15-LOX) is an enzyme, which oxidizes polyunsaturated fatty acids, particularly omega-6 and −3 fatty acids, to generate a number of bioactive lipid metabolites. A large number of studies have revealed the importance of 12/15-LOX role in oxidative and inflammatory responses. The in vitro studies have demonstrated the ability of 12/15-LOX metabolites in the expression of various genes and production of cytokine related to inflammation and resolution of inflammation. The studies with the use of knockout and transgenic animals for 12/15-LOX have further shown its involvement in the pathogenesis of a variety of human diseases, including cardiovascular, renal, neurological and metabolic disorders. This review summarizes our current knowledge on the role of 12/15-LOX in inflammation and various human diseases.

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Activation of the 12/15 lipoxygenase pathway accompanies metabolic decline in db/db pre-diabetic mice

Cited by 13 publications

References 55 publications

Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications

Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications

5-Lipooxygenase Derivatives as Serum Biomarkers of a Successful Dietary Intervention in Patients with NonAlcoholic Fatty Liver Disease

Emerging role of 12/15-Lipoxygenase (ALOX15) in human pathologies

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