Reduction of inflammation and chronic tissue damage by omega-3 fatty acids in fat-1 transgenic mice with pancreatitis

Abstract

Summary Pancreatitis is a severe debilitating disease with high morbidity and mortality. Treatment is mostly supportive, and until now there are no clinically useful strategies for anti-inflammatory therapy. Although omega-3 polyunsaturated fatty acids (n-3 PUFA) are known to have anti-inflammatory effects, the utility of these fatty acids in the alleviation of pancreatitis remained to be investigated. The aim of this study was to examine the effect of n-3 PUFA on both acute and chronic pancreatitis in a well-controlled experimental system. We used the fat-1 transgenic mouse model, characterised by endogenously increased tissue levels of n-3 PUFA, and their wild-type littermates to examine the effect of n-3 PUFA on both acute and chronic cerulein induced pancreatitis. Disease activity and inflammatory status were assessed by both histology and molecular methods. In acute pancreatitis, fat-1 mice showed a trend towards decreased necrosis and significantly reduced levels of plasma IL-6 levels as well as reduced neutrophil infiltration in the lung. In chronic pancreatitis there was less pancreatic fibrosis and collagen content accompanied by decreased pancreatic stellate cell activation in the fat-1 animals with increased n-3 PUFA tissue levels as compared to wild-type littermates with high levels of omega-6 (n-6) PUFA in their tissues. Our data provide evidence for a reduction of systemic inflammation in acute pancreatitis and of tissue fibrosis in chronic pancreatitis by increasing the tissue content of omega-3 polyunsaturated fatty acids. These results suggest a beneficial potential for n-3 PUFA supplementation in acute and particularly chronic pancreatitis.

Transgenic conversion of omega-6 into omega-3 fatty acids in a mouse model of Parkinson's disease

“…Clues that the fat-1 transgene has an anti-infl ammatory activity were also given by reports that brain COX-2 levels are reduced in 12-week-old Fat-1 mice ( 33 ). This dampening of the infl ammatory response was also associated with a benefi cial effect as observed in Fat-1 modeling pancreatitis and infl amed colon ( 54,55 ). Finally, the decrease in GFAP levels observed here in Fat-1 mice following MPTP lesion supports the hypothesis of an anti-infl ammatory role for the fat-1 transgene despite the absence of a clear neuroprotective effect.…”

Article: Eicosapentaenoic Acid Blocks Cyclosporine A-Induced Pancreatic Dysfunction but not Immunosuppression

“…These results suggest that EPA does not alter the ability of CsA to inhibit NFATc3 nuclear translocation, and, hence, does not impede immunosuppression by CsA. Although several studies have shown that omega-3 PUFAs have antioxidant and antiinflammatory effects (Gómez et al, 2004;Weylandt et al, 2008), the present work demonstrates for the first time that EPA treatment reverses damage to pancreatic islet cells caused by long-term administration of CsA in rats. Blood glucose levels increased 30 min after injection of glucose and returned to the baseline value after 180 min in all rats.…”

“…The search for drugs that can ameliorate CsA-induced adverse side effects related to glucose intolerance is on-going. Omega-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA), have antioxidant properties and anti-inflammatory activity, and thus have beneficial effects on cardiovascular health (Shimojo et al, 2006;Weylandt et al, 2008;Oh et al, 2010).…”

The use of genetic engineering techniques to improve the lipid composition in meat, milk and fish products: a review

“…It was found that the high expression of these acids in various tissues of transgenic mice had therapeutic potential and inhibited the development of many experimentally provoked illnesses, that is colitis (Hudert et al, 2006;Gravaghi et al, 2011), colon cancer (Nowak et al, 2007;Jia et al, 2008), breast cancer (Reddy et al, 2012;Zou et al, 2013), melanoma (Xia et al, 2006), neoplasia (Griffitts et al, 2010), liver tumour , pancreatitis (Weylandt et al, 2008), diabetes (Bellenger et al, 2011), stroke (Hu et al, 2013), age-related glucose intolerance (Romanatto et al, 2014), fatty liver disease (Kim et al, 2012), osteoporosis (Rahman et al, 2009a), asthma , spinal cord injury and epilepsy (Taha et al, 2008). Moreover, increased endogenous synthesis of n-3 LCPUFAs had a beneficial effect on spatial learning performance (He et al, 2009), as well as attenuation of inflammation processes and Figure 1 Scheme of long-chain n-3 polyunsaturated fatty acids (LCPUFAs) synthesis patchway indicating the role of the enzymes which were introduced in the different transgenic models.…”