Einfluß erhitzter Fette auf peroxisome proliferator-activated rreceptor gamma (PPARy)-regulierte metabolische und zelluläre Prozesse im Schwein als Modelltier für den Menschen
Final Report Abstract
The main hypothesis of this proposal was that feeding of a heated fat causes PPARγ activation in different tissues of pigs as model objects for humans, and, thereby, provokes different biological effects that are regulated by PPARγ. The results from two feeding experiments with pigs (metalipox 1, metalipox 2) strongly suggest that oxidized fat is not a significant activator of PPARγ in vivo. However, the results from “metalipox 2” confirm findings from recent studies in several animal species that oxidized fat is a potent activator of PPARα. Furthermore the results from this project show that oxidized fats as important components of the Western diet provoke several biological effects in the organism. Novel biological effects of oxidized fat identified in this project are the increased release of FGF21 – a metabolic regulator playing a crucial role in glucose homeostasis, lipid metabolism, insulin sensitivity and obesity, and the activation of NF-κB and Nrf2 signaling pathways. Both pathways are involved in stress response and activation of NF-κB and Nrf2 signaling is generally regarded as a beneficial effect as it causes an upregulation of a wide spectrum of antioxidant, cytoprotective and detoxifying genes and thus protects the cell against ROS and toxic compounds. A further interesting and novel finding was obtained from an additional experiment with a mouse model of atherosclerosis. In this model convincing evidence was provided to suggest that oxidized fat exerts antiatherogenic effects by activation of PPARα in both the liver, which contributes to lipid lowering in plasma, and in the vasculature, which inhibits proatherogenic events such as monocyte recruitment and smooth muscle cell proliferation and migration. Collectively, the results from the present project show that oxidized fats prepared under practical conditions in human nutrition cause profound biological effects in pigs. Given the strong similarities between pigs and humans with respect to digestive tract physiology, lipid metabolism, and the expression levels of PPARs, it is not unlikely that a dietary regime rich in fried foods containing oxidized fats causes similar effects in humans. Regarding several beneficial effects of oxidized fats identified in this project, it has to be mentioned that the results must not be interpreted in that way that oxidized fats are generally regarded as a health-promoting component of the diet as components of oxidized fats have several adverse effects in humans. The results of this study rather suggest that oxidized fats are a mixture of chemically distinct substances, some of which exhibit a significant biological activity.
Publications
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(2010) Health aspects of oxidized fats. In: E Decker, R Elias, D J McClements (eds), Woodhead Publishing, Oxidation in foods and beverages and antioxidant applications. Volume 1: Understanding mechanisms of oxidation and antioxidant activity. pp. 143-180
Eder K, Ringseis R
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(2011) 13-hydroxy linoleic acid increases expression of the cholesterol transporters ABCA1, ABCG1 and SR-BI and stimulates apoA-I-dependent cholesterol efflux in RAW264.7 macrophages. Lipids in Health and Disease 10: 222
Kämmerer I, Ringseis R, Biemann R, Wen G, Eder K
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(2011) Dietary oxidized fat activates the oxidative stress-responsive transcription factors NF-κB and Nrf2 in intestinal mucosa of mice. European Journal of Nutrition 50: 601-609
Varady J, Eder K, Ringseis R
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(2011) Feeding a thermally oxidised fat inhibits atherosclerotic plaque formation in the aortic root of LDL receptor-deficient mice. British Journal of Nutrition 105: 190-199
Kämmerer I, Ringseis R, Eder K
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(2011) Regulation of genes involved in lipid metabolism by dietary oxidized fat. Molecular Nutrition Food Research 55: 109-121
Ringseis R, Eder K
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(2012) Dietary moderately oxidized oil activates the Nrf2 signaling pathway in the liver of pigs. Lipids in Health and Disease 11: 31
Varady J, Gessner DK, Most E, Eder K, Ringseis R
