- Obesity is also an important risk factor for a number of health conditions including diabetes and cardiovascular disease.
- Fatty liver disease is a condition where large amounts of fat accumulate in liver cells and is characteristic of metabolic syndrome. (Wipedia)
High fat diets decrease PGC-1a which is important for metabolic cellular processes, mitochondrial biogenesis and mitochondrial DNA synthesis. In addition, it decreases the expression of Nrf2 which is the master gene promoter that upregulates expression of genes important for the same process. The PGC-1a complex also controls another protein called Foxo3a which is an important modulator of aging. (Dong)
In addition to playing a role in redox homeostasis, Nrf2 modulates inflammatory mediators such as Tnf-a and MCP-1 and prevents lipid accumulation. Nrf2 is activated in response to toxicant injury and oxidative stress and is important for the detoxification of xenobiotics.
Tanaka's studies have shown the absence of Nrf2 increases susceptibility to toxicants including acetaminophen, hyperoxia, benzopyrene (found in smoke). He demonstrated that Nrf2 has important lipid metabolism and that feeding a high fat diet in the short term reduces Nrf2. He notes, other studies have shown long-term feeding of high fat diets increases Nrf2 and suggests this is an adapative response to oxidative stress induced by chronic fat accumulation. Generally, animals with lower Nrf2 present with elevated cholesterol levels and lower levels of Nrf2 results in the inability to prevent lipid accumulation, absence leads to greater retention of lipids in the liver (fatty liver disease) and greater oxidative stress including, oxidative stress in the mitochondria and the endoplasmic reticulum. Interestingly, Tanaka found that PGC-1a is reduced in high-fat diets but not in Nrf2 null mice which indicates the down-regulation of PGC-1a is dependant on Nrf2.
Summary: High fat diets reduce mitochondrial biogenesis, increases the likelihood for toxicant bioaccumulation and their overall toxic effects, increases oxidative stress, contributes to fat accumulation and obesity and impairs liver function which is an important organ for detoxification.
Dong, F., Li, Q., Sreejayan, N., Nunn, J. M., and Ren, J. (2007). Metallothionein prevents high-fat diet–induced cardiac contractile dysfunction role of peroxisome proliferator–activated receptor coactivator 1 and mitochondrial biogenesis. 56(9):2201-2212. http://www.citeulike.org/user/HEIRS/article/5724999
Tanaka, Y., Aleksunes, L. M., Yeager, R. L., Gyamfi, M. A., Esterly, N., Guo, G. L., and Klaassen, C. D. (2008). Nf-e2-related factor 2 inhibits lipid accumulation and oxidative stress in mice fed a high-fat diet. J Pharmacol Exp Ther, 325(2):655-664. http://www.citeulike.org/user/HEIRS/article/4788030
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