What Fatty Acids We Eat
in [Diabetes]
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From: ironjustice on 27 Sep 2008 19:46 Discovery offers new understanding of diabetes drug target September 26, 2008 Team from University of Leicester reveal how the protein PPAR gamma binds to 8 fatty acids Scientists at the University of Leicester have published findings about a new advance in the study of major diabetes drug target. The advance - described by the researchers as 'very significant' - could lead to new drugs being developed to target a protein that plays a critical role in controlling the way the body breaks down sugar. Professor John Schwabe and his team from the University of Leicester Department of Biochemistry (together with teams from Japan and Hungary) have been studying the protein, PPAR gamma. PPAR gamma is a major drug target for the treatment of type 2 diabetes. Although it was known how drugs are able to activate this protein, until this study, using the sophisticated technique of X-ray Crystallography, it was not clear how PPAR gamma is naturally activated in the body. X-ray Crystallography is the principal method by which the detailed 3- dimensional structures of molecules - especially the molecules of living systems - have been discovered. It is achieved by firing X-rays at the target and creating its structures by analysing how the x-rays scatter into many different directions. Through this method, the Leicester team have shown how PPAR gamma binds to eight different fatty acids, derived in part from what we eat. They found that many of these acids joined irreversibly with the protein and led to its long term activation. They have also shown that sometimes two fatty acids bind simultaneously, which might mean that PPAR gamma could be targeted by a mixture of drugs. Professor John Schwabe, who led the Leicester project with his team, including Dr Toshimasa Itoh and Dr Louise Fairall, said: "The finding that natural activators for PPAR gamma couple irreversibly to the PPAR gamma receptor dramatically changes our understanding of how this receptor is activated. "It may also allow for the design of novel pharmaceuticals that give longer term activation of PPAR gamma, at lower doses, without some of the side effects of the current generation of drugs." Professor Schwabe said: "PPAR gamma is a critical player in the increasingly prevalent metabolic disease of type 2 diabetes which affects more than 180 million people worldwide (World Health Organisisation) and in the UK alone costs the NHS £9.6 million every day. "PPARgamma is activated by two widely prescribed anti-diabetic insulin- sensitising drugs, Actos and Avandia. However the identity of the natural activators for PPAR gamma has remained unclear. "Our breakthrough is important because it reveals for the first time that how this protein is activated by naturally-occuring fatty acids. This knowledge will help in the design of future novel pharmaceutical agents." University of Leicester Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
From: ironjustice on 28 Sep 2008 00:14 On Sep 27, 4:46 pm, "ironjust...(a)aol.com" <ironjust...(a)aol.com> wrote:Team from University of Leicester reveal how the protein PPAR gamma binds to 8 fatty acids << http://tinyurl.com/3gc6s8 Therefore, this hypothesis bridges the concept of natural PPAR agonists and the use of structural information in designing new drugs against diabetes and metabolic syndrome. The derivatives may also be used as anti-inflammatory and anticancer agents. PMID: 18355413 ----------------------- Sci. STKE, 28 November 2006 Vol. 2006, Issue 363, p. tw401 [DOI: 10.1126/stke.3632006tw401] EDITORS' CHOICE Immunology Nitrated Fatty Acids as Signaling Molecules L. Bryan Ray Science, Sciences STKE, AAAS, Washington, DC 20005, USA Some fatty acid derivatives, like prostaglandins and thromboxanes, are well known signaling molecules. A more recently recognized, related class of molecules that could have similar functions includes the nitration products of unsaturated fatty acids (nitroalkenes) formed in nitric oxide (NO)-dependent oxidative reactions. In particular, the nitroalkene derivatives of linoleic acid (LNO2) and oleic acid (OA-NO2) are found in human plasma and are thought to regulate physiological functions in multiple cell types. Rather than binding to receptors, though, these molecules are proposed to act by mediating reversible nitroalkylation of glutathione or of Cys or His residues of proteins. Cui et al. now report experiments indicating that LNO2 and OA-NO2 may function as antiinflammatory agents. The authors applied concentrations of LNO2 and OA-NO2 similar to those found in human blood to cultured mouse macrophages and observed dose- dependent decreases in lipopolysaccharide (LPS)-induced cytokine secretion by the cells. The transcription factor NF-B has a central role in inflammatory responses, and treatment of macrophages with LNO2 or OA-NO2 decreased activation of the transcription factor in response to LPS. Experiments with biotinylated LNO2, OA-NO2, LA (linoleic acid), and OA indicated that LNO2 and OA-NO2, but not LA or OA, associated with the p65 subunit of NF-B and appeared to modify p65 by covalent nitroalkylation. The nitroalkenes also inhibited adhesion of monocytes to endothelial cells in culture. The authors propose that nitroalkenes like LNO2 and OA-NO2 may prove to be an important class of signaling molecules influencing inflammatory processes. T. Cui, F. J. Schopfer, J. Zhang, K. Chen, T. Ichikawa, P. R. S. Baker, C. Batthyany, B. K. Chacko, X. Feng, R. P. Patel, A. Agarwal, B. A. Freeman, Y. E. Chen, Nitrated fatty acids: Endogenous anti- inflammatory signaling mediators. J. Biol. Chem. 281, 35686-35698 (2006). [Abstract] [Full Text] Citation: L. B. Ray, Nitrated Fatty Acids as Signaling Molecules. Sci. STKE 2006, tw401 (2006). University of Leicester Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > Discovery offers new understanding of diabetes drug target > September 26, 2008 > > Team from University of Leicester reveal how the protein PPAR gamma > binds to 8 fatty acids > > Scientists at the University of Leicester have published findings > about a new advance in the study of major diabetes drug target. > > The advance - described by the researchers as 'very significant' - > could lead to new drugs being developed to target a protein that plays > a critical role in controlling the way the body breaks down sugar. > > Professor John Schwabe and his team from the University of Leicester > Department of Biochemistry (together with teams from Japan and > Hungary) have been studying the protein, PPAR gamma. PPAR gamma is a > major drug target for the treatment of type 2 diabetes. Although it > was known how drugs are able to activate this protein, until this > study, using the sophisticated technique of X-ray Crystallography, it > was not clear how PPAR gamma is naturally activated in the body. > > X-ray Crystallography is the principal method by which the detailed 3- > dimensional structures of molecules - especially the molecules of > living systems - have been discovered. It is achieved by firing X-rays > at the target and creating its structures by analysing how the x-rays > scatter into many different directions. > > Through this method, the Leicester team have shown how PPAR gamma > binds to eight different fatty acids, derived in part from what we > eat. They found that many of these acids joined irreversibly with the > protein and led to its long term activation. They have also shown that > sometimes two fatty acids bind simultaneously, which might mean that > PPAR gamma could be targeted by a mixture of drugs. > > Professor John Schwabe, who led the Leicester project with his team, > including Dr Toshimasa Itoh and Dr Louise Fairall, said: "The finding > that natural activators for PPAR gamma couple irreversibly to the PPAR > gamma receptor dramatically changes our understanding of how this > receptor is activated. > > "It may also allow for the design of novel pharmaceuticals that give > longer term activation of PPAR gamma, at lower doses, without some of > the side effects of the current generation of drugs." > > Professor Schwabe said: "PPAR gamma is a critical player in the > increasingly prevalent metabolic disease of type 2 diabetes which > affects more than 180 million people worldwide (World Health > Organisisation) and in the UK alone costs the NHS £9.6 million every > day. > > "PPARgamma is activated by two widely prescribed anti-diabetic > insulin- sensitising drugs, Actos and Avandia. However the identity of > the natural activators for PPAR gamma has remained unclear. > > "Our breakthrough is important because it reveals for the first time > that how this protein is activated by naturally-occuring fatty acids. > This knowledge will help in the design of future novel pharmaceutical > agents." > > University of Leicester > > Who loves ya. > Tom > > Jesus Was A Vegetarian!http://tinyurl.com/2r2nkh > > Man Is A Herbivore!http://tinyurl.com/a3cc3 > > DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk
From: ironjustice on 28 Sep 2008 00:46 On Sep 27, 9:14 pm, ironjustice <teamtan...(a)hotmail.com> wrote:the concept of natural PPAR agonists << "Supplementation of flaxseed flour, a source of omega-3 fatty acids for 2 weeks" Systemic inflammation in morbidly obese subjects: response to oral supplementation with alpha-linolenic acid Alternative Medicine Review, Sept, 2007 by J. Faintuch, L.M. Horie, H.V. Barbeiro BACKGROUND: Morbidly obese patients frequently display asymptomatic chronic activation of acute phase response, with potentially adverse metabolic and cardiovascular consequences. Nutritional preparations to improve this phenomenon have rarely been administered. Aiming to investigate the supplementation of flaxseed flour, a source of omega-3 fatty acids, a prospective randomized double-blind cross-over study was designed. METHODS: Outpatient obese subjects (n = 41) were clinically and biochemically screened, and results for 24 randomized subjects are shown. Age was 40.8 +/- 11.6 years (83.3% females) and body mass index (BMI) was 47.1 +/- 7.2 kg/ [m.sup.2]. Flaxseed flour (Farinha de Linhaca Dourada LinoLive, Cisbra, Brazil) in the amount of 30 g/day (5 g of alphalinolenic acid - omega-3) and an equal mass of placebo (manioc flour) were administered for 2 weeks each. Variables included general biochemical investigation, white blood cell count (WBC), C-reactive protein (CRP), serum amyloid A (SAA) and fibronectin. RESULTS: No intolerance was registered. Body weight and general biochemical indices remained stable. Initial CRP and SAA were elevated (13.7 +/- 9.9 and 17.4 +/- 8.0 ).WBC (8100 +/- 2100/[mm.sup.3]) and fibronectin (463.2 +/- 61.3 mg/dL) were acceptable but in the upper normal range. Corresponding findings after supplementation of flaxseed were 10.6 +/- 6.2 mg/L, 14.3 +/- 9.2 mg/L, 7300 +/- 1800/[mm.sup.3] and 412.8 +/- 38.6 respectively (P<0.05). No change during the control period regarding baseline occurred when placebo was randomized to be given first; however, when it followed omega-3 supplementation, CRP and SAA recovered, whereas WBC and fibronection remained depressed during those 2 weeks (7500 +/- 2100/ [mm.sup.3] and 393.2 +/- 75.8 mg/dL, P<0.05). CONCLUSIONS: 1) Various inflammatory markers were elevated in the studied population, although not necessarily exceeding the normal range; 2) Significant reduction could be demonstrated; 3) Some persistent effects of flaxseed supplement 2 weeks after discontinuation were observed. ------------------ Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > On Sep 27, 4:46 pm, "ironjust...(a)aol.com" <ironjust...(a)aol.com> > wrote:Team from University of Leicester reveal how the protein PPAR > gamma binds to 8 fatty acids << > > http://tinyurl.com/3gc6s8 > > Therefore, this hypothesis bridges the concept of natural PPAR > agonists and the use of structural information in designing new drugs > against diabetes and metabolic syndrome. > The derivatives may also be used as anti-inflammatory and anticancer > agents. > > PMID: 18355413 > ----------------------- > > Sci. STKE, 28 November 2006 > Vol. 2006, Issue 363, p. tw401 > [DOI: 10.1126/stke.3632006tw401] > > EDITORS' CHOICE > Immunology > Nitrated Fatty Acids as Signaling Molecules > L. Bryan Ray > > Science, Sciences STKE, AAAS, Washington, DC 20005, USA > > Some fatty acid derivatives, like prostaglandins and thromboxanes, are > well known signaling molecules. > A more recently recognized, related class of molecules that could have > similar functions includes the nitration products of unsaturated fatty > acids (nitroalkenes) formed in nitric oxide (NO)-dependent oxidative > reactions. > In particular, the nitroalkene derivatives of linoleic acid (LNO2) and > oleic acid (OA-NO2) are found in human plasma and are thought to > regulate physiological functions in multiple cell types. > Rather than binding to receptors, though, these molecules are proposed > to act by mediating reversible nitroalkylation of glutathione or of > Cys or His residues of proteins. > Cui et al. now report experiments indicating that LNO2 and OA-NO2 may > function as antiinflammatory agents. > The authors applied concentrations of LNO2 and OA-NO2 similar to those > found in human blood to cultured mouse macrophages and observed dose- > dependent decreases in lipopolysaccharide (LPS)-induced cytokine > secretion by the cells. The transcription factor NF-B has a central > role in inflammatory responses, and treatment of macrophages with LNO2 > or OA-NO2 decreased activation of the transcription factor in response > to LPS. > Experiments with biotinylated LNO2, OA-NO2, LA (linoleic acid), and OA > indicated that LNO2 and OA-NO2, but not LA or OA, associated with the > p65 subunit of NF-B and appeared to modify p65 by covalent > nitroalkylation. > The nitroalkenes also inhibited adhesion of monocytes to endothelial > cells in culture. > The authors propose that nitroalkenes like LNO2 and OA-NO2 may prove > to be an important class of signaling molecules influencing > inflammatory processes. > > T. Cui, F. J. Schopfer, J. Zhang, K. Chen, T. Ichikawa, P. R. S. > Baker, C. Batthyany, B. K. Chacko, X. Feng, R. P. Patel, A. Agarwal, > B. A. Freeman, Y. E. Chen, Nitrated fatty acids: Endogenous anti- > inflammatory signaling mediators. J. Biol. Chem. 281, 35686-35698 > (2006). [Abstract] [Full Text] > > Citation: L. B. Ray, Nitrated Fatty Acids as Signaling Molecules. Sci. > STKE 2006, tw401 (2006). > > University of Leicester > > Who loves ya. > Tom > > Jesus Was A Vegetarian!http://tinyurl.com/2r2nkh > > Man Is A Herbivore!http://tinyurl.com/a3cc3 > > DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk > > > > > Discovery offers new understanding of diabetes drug target > > September 26, 2008 > > > Team from University of Leicester reveal how the protein PPAR gamma > > binds to 8 fatty acids > > > Scientists at the University of Leicester have published findings > > about a new advance in the study of major diabetes drug target. > > > The advance - described by the researchers as 'very significant' - > > could lead to new drugs being developed to target a protein that plays > > a critical role in controlling the way the body breaks down sugar. > > > Professor John Schwabe and his team from the University of Leicester > > Department of Biochemistry (together with teams from Japan and > > Hungary) have been studying the protein, PPAR gamma. PPAR gamma is a > > major drug target for the treatment of type 2 diabetes. Although it > > was known how drugs are able to activate this protein, until this > > study, using the sophisticated technique of X-ray Crystallography, it > > was not clear how PPAR gamma is naturally activated in the body. > > > X-ray Crystallography is the principal method by which the detailed 3- > > dimensional structures of molecules - especially the molecules of > > living systems - have been discovered. It is achieved by firing X-rays > > at the target and creating its structures by analysing how the x-rays > > scatter into many different directions. > > > Through this method, the Leicester team have shown how PPAR gamma > > binds to eight different fatty acids, derived in part from what we > > eat. They found that many of these acids joined irreversibly with the > > protein and led to its long term activation. They have also shown that > > sometimes two fatty acids bind simultaneously, which might mean that > > PPAR gamma could be targeted by a mixture of drugs. > > > Professor John Schwabe, who led the Leicester project with his team, > > including Dr Toshimasa Itoh and Dr Louise Fairall, said: "The finding > > that natural activators for PPAR gamma couple irreversibly to the PPAR > > gamma receptor dramatically changes our understanding of how this > > receptor is activated. > > > "It may also allow for the design of novel pharmaceuticals that give > > longer term activation of PPAR gamma, at lower doses, without some of > > the side effects of the current generation of drugs." > > > Professor Schwabe said: "PPAR gamma is a critical player in the > > increasingly prevalent metabolic disease of type 2 diabetes which > > affects more than 180 million people worldwide (World Health > > Organisisation) and in the UK alone costs the NHS £9.6 million every > > day. > > > "PPARgamma is activated by two widely prescribed anti-diabetic > > insulin- sensitising drugs, Actos and Avandia. However the identity of > > the natural activators for PPAR gamma has remained unclear. > > > "Our breakthrough is important because it reveals for the first time > > that how this protein is activated by naturally-occuring fatty acids. > > This knowledge will help in the design of future novel pharmaceutical > > agents." > > > University of Leicester > > > Who loves ya. > > Tom > > > Jesus Was A Vegetarian!http://tinyurl.com/2r2nkh > > > Man Is A Herbivore!http://tinyurl.com/a3cc3 > > > DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk- Hide quoted text - > > - Show quoted text -
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