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"PPAR modulators are drugs which act upon the peroxisome proliferator-activated receptor."

"Summer vs Winter Mode: Explaining AMPK Last year I read an article which made a statement that has not left my mind. The statement went as follows: "You are only good as your mitochondria." In fact, the more a dwell into the details of human metabolism, the more I sense that this is true - especially with the metabolic syndrome. For those who are not familiar with the concept of mitochondria, they are the tiny energy factories within the cells that produce cellular energy through aerobic means (meaning oxygen). Mitochondria utilize oxygen to ultimately produce Adenosine Triphosphate or simply ATP. ATP relays energy by donating a phosphate bond resulting in Adenosine Diphosphate (ADP). Another phosphate release would entail Adenosine Monophosphate or AMP. ATP is one of the main sources of cellular energy in the body

In the field of molecular biology, the peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes.[1] PPARs play essential roles in the regulation of cellular differentiation, development, and metabolism (carbohydrate, lipid, protein), and tumorigenesis[2] of higher organism.

These data indicate that fish oil feeding downregulated the endogenous PPAR-activation system and increased antioxidant gene expressions to protect against ROS excess Fish oil feeding alters liver gene expressions to defend against PPARalpha activation and ROS production. Takahashi M, Tsuboyama-Kasaoka N, Nakatani T, Ishii M, Tsutsumi S, Aburatani H, Ezaki O. Am J Physiol Gastrointest Liver Physiol. 2002 Feb;282(2):G338-48. PMID: 11804856

Docosahexaenoic acid inhibits superoxide dismutase 1 gene transcription in human cancer cells: the involvement of peroxisome proliferator-activated receptor alpha and hypoxia-inducible factor-2alpha signaling. Tuller ER, Beavers CT, Lou JR, Ihnat MA, Benbrook DM, Ding WQ. Mol Pharmacol. 2009 Sep;76(3):588-95. Epub 2009 Jun 15. PMID: 19528198

According to Dr. Willcox, Principal Investor for the Okinawa Centenarian Study that started in 1975, "Among the entire population, which takes a sparing approach to food, there is 90 percent less coronary artery disease than in the wider world, a third less incidence of cancer, and breast cancer is virtually unheard of." HERE. In long-living Okinawan and Japanese, their dietary intake as surveyed in the 1970s was higher in both protein and dietary saturated fatty acids (see below abstract) compared to their shorter-lived peers at that time. When Okinawans move away (like to Brazil) heart disease risk factors appear (see last abstract). Diet is 80-90% of our health I believe because our bodies are designed to express what is dictated by our environment and food macro- micronutrients (foraging/hunting v. lounging; fecundity v. fasting). (These are the PPAR alpha gamma and delta receptors; their role is to 'sense nutrients' and to 'sense energy demand' in order to ultimately balance our energy needs). To me, the observations from blue zones and centenarian data always seem to reinforce that the physically active, low carb mod-high fat Paleo/TYP approach is the most optimal at this time, as it was for centenarians studied in the 1970s.

Conjugated linoleic acid promotes human adipocyte insulin resistance through NFkappaB-dependent cytokine production. Chung S, Brown JM, Provo JN, Hopkins R, McIntosh MK. J Biol Chem. 2005 Nov 18;280(46):38445-56. Epub 2005 Sep 9. PMID: 16155293 doi: 10.1074/jbc.M508159200 Collectively, these data demonstrate for the first time that trans-10, cis-12 CLA promotes NFkappaB activation and subsequent induction of IL-6, which are at least in part responsible for trans-10, cis-12 CLA-mediated suppression of peroxisome proliferator-activated receptor gamma target gene expression and insulin sensitivity in mature human adipocytes. In summary, our in vitro data demonstrate that a physiological level of trans-10, cis-12 CLA activates NFκB- and ERK1/2-dependent cytokine production, which together suppress PPARγ and Glut4 levels and lead to impaired glucose uptake. Studies are currently under way examining 1) how CLA regulates PPARγ and the expression of its target genes, 2) the specific signaling role of SV cells and adipocytes in mediating the TG-lowering actions of CLA, and 3) the CLA-induced, upstream signal that activates NFκB and ERK1/2.

n-3 fatty acids and gene expression. Deckelbaum RJ, Worgall TS, Seo T. Am J Clin Nutr. 2006 Jun;83(6 Suppl):1520S-1525S. Review. Erratum in: Am J Clin Nutr. 2006 Oct;84(4):949. PMID: 16841862 Accumulating evidence in both humans and animal models clearly indicates that a group of very-long-chain polyunsaturated fatty acids, the n-3 fatty acids (or omega-3), have distinct and important bioactive properties compared with other groups of fatty acids. n-3 Fatty acids are known to reduce many risk factors associated with several diseases, such as cardiovascular diseases, diabetes, and cancer. The mechanisms whereby n-3 fatty acids affect gene expression are complex and involve multiple processes. As examples, n-3 fatty acids regulate 2 groups of transcription factors, such as sterol-regulatory-element binding proteins and peroxisome proliferator-activated receptors, that are critical for modulating the expression of genes controlling both systemic and tissue-specific lipid homeostasis. Modulation of specific genes by n-3 fatty acids and cross-talk between these genes are responsible for many effects of n-3 fatty acids.