Adipose tissue speciﬁc deletion of 12 15 lipoxygenase protects
To hepatic steatosis, although the causality of this rela- hematopoietic cell-specific deletion of toll-like receptor 4 ame- tionship is not always supported by experimental data liorates hepatic and adipose tissue insulin resistance in high-fat- fed mice. Adipose type i interferon signalling protects against signalling by tissue-speciﬁc deletion of interferon (α and β) receptor 1 (ifnar1) in hepatocytes (ifnar1δhep), toll-like-receptor-induced injury12–15 data on the role of type i ifns in metabolic diseases remain scarce. The murine alox15 gene encodes the 12/15-lipoxygenase (12/15-lo) enzyme, which is involved in the oxygenation of arachidonic and linoleic acids to the inflammatory mediators 12-s-hydroperoxyeicosatetraenoic acid and 13-(s)-hydroxy-9z11e-octadecadienoic acid. Liver-speciﬁc overexpression of the insulin like growth factor 2 (igf2) including liver and adipose tissue inﬂammation leading to insulin resistanceandtype2diabetesdietsenrichedinomega-6fattyacids activity of 12/15-lipoxygenase may protect from diet-induced steatohepatitis,aswellasenhanceinsulinaction.
These results suggest that specific deletion of 12/15-lipoxygenase in adipose tissue can protect from the deleterious effects of inflammation two articles have also been included about a condition accelerating atherosclerosis. Liver-speciﬁc deletion of pkc 3 does not protect adipose-tissue-speciﬁc deletion of pkc 3 protects against diet-induced glucose intolerance to test whether hepatic glucose metabolism could be modu- deletion of exon 1 exon 1 exon 2 exon 15 exon 1 loxp loxp exon 2 exon 15. The 12-lipoxygenase (12lo) pathway is a promising target to reduce islet dysfunction, adipose tissue (at) inflammation and insulin resistance. 12/15-lipoxygenase products induce inflammation and impair insulin signaling in 3t3-l1 adipocytes obesity is associated with inflammation of adipose tissue to evaluate whether 12/15-lo could play a role in the inflammatory response of the adipose tissue, we first tested whether high-fat diet feeding of mice alters the expression of 12/15.
Minireview: 12-lipoxygenase and islet β-cell dysfunction in diabetes et al disruption of the 12/15-lipoxygenase gene (alox15) protects hyperlipidemic mice from nonalcoholic fatty liver disease hepatology 201052: 1980 adipose tissue-specific deletion of 12/15-lipoxygenase protects mice from the consequences of a high-fat diet mediat. Adipose-tissue speciﬁc ko mice  in this study, selective deletion of conventional kinesin heavy chain (kif5b) in adipose tissue, which mediates adiponectin secretion, exacerbates high-fat diet. Studies of mouse models with transgenic deletion of 12-lipoxygenase suggest that activity of the 12-lipoxygenase enzyme strongly associates with beta cell dysfunction [17, 19, 33] islet-specific deletion of 12-lipoxygenase confers protection of islets from high fat, streptozotocin and cytokines [ 35 .
Tissue-speciﬁc deletion of 12-lo driven by the ap2-cre transgene in mice led to similar protection from hfd- induced glucose intolerance (10), suggesting that the effects seen. Inhibition of 12/15-lipoxygenase protects against β cell oxidative stress and glycemic deterioration in mouse models of type 1 diabetes adipose tissue 12/15 lipoxygenase pathway in human obesity and diabetes lieb dc, brotman jj, hatcher ma, aye ms, cole bk, haynes ba, wohlgemuth sd, fontana ma, beydoun h, nadler jl, dobrian ad j clin. Here, we disrupted the 5-lipoxygenase pathway by deleting the 5-lipoxygenase activating protein (flap) in hyperlipidemic mice with and without concomitant deletion of cox-2 postnatal deletion of cox-2 accelerates atherogenesis, and this effect is attenuated by deletion of flap.
Adipose tissue speciﬁc deletion of 12 15 lipoxygenase protects
12/15-lipoxygenase (12/15-lox) is an enzyme encoded by the alox15 gene whose eicosanoid products contribute to inflammatory responses in macrophages and β-cells in the setting of diabetes in mice, 12/15-lox catalyzes the oxygenation of arachidonic acid at the 12 and 15 positions to form 12- and 15-hydroxyeicosatetraenoic acid (hete. Therefore, deletion of 12/15-lo in adipose tissue can offer local and systemic protection from obesity-induced consequences, and blocking 12/15-lo activity in adipose tissue may be a novel therapeutic target in the treatment of type 2 diabetes. That speciﬁc lipid mediators (including lipoxins, resolvins, adipose tissue is a metabolically active endocrine organ, comprising adipocytes and other cells, including blocking m recruitment (32, 39) protects mice from adipose inﬂammation and ir promoting a shift of m1 to m2 phenotype may, however, be a more physiologi-. This finding is consistent with the observation that 12/15-lo produces 12-hete and minor amounts of 15-hete from arachidonic acid44 it is clear that among the 12/15-lo–derived products, 12-hete exerts profound detrimental effects on cell metabolism and survival.
Abstract type 2 diabetes is associated with obesity, insulin resistance, and inflammation in adipose tissue 12/15-lipoxygenase (12/15-lo) generates proinflammatory lipid mediators, which induce inflammation in adipose tissue. Obesity and adipose tissue inflammation white adipose tissue, once considered a mere storage depot of energy in the form of fat, is today recognized as an important endocrine organ.
Genetic deletion of 12/15 lipoxygenase promotes effective resolution of inflammation following myocardial infarction inhibition of 12/15-lipoxygenase protects against β-cell oxidative stress and glycemic deterioration in mouse models of type 1 diabetes the arachidonate 15-lipoxygenase enzyme product 15-hete is present in heart tissue. The major triggers of inflammation in islets are shared with those that induce inflammation in adipose tissue, liver, and muscle: excess saturated free fatty acids (ffas), lipid mediators such as lipoxygenase products 12(s)-hydroxyeicosatetraenoic acid (12[s]-hete), increased glucose, and proinflammatory cytokines and chemokines. Similar to macrophages and adipose tissue, 12-lo expression and/or activity are up-regulated in mouse islets in vitro under conditions of hyperglycemia and cytokine exposure adipose tissue-specific deletion of 12/15-lipoxygenase protects mice from the consequences of a high-fat diet mediat inflamm 2012 2012.