Which Samurai with his spunky
Eating is definitely a sensory activity that starts with the brain-- have you heard that saying 'eating with your eyes'? Have you ever given your liver much thought while you consuming your meals or snacks? Ever wonder where does the food go before it hits the bloodstream?
In fact, the human liver is the largest internal organ comprising of 3 lobes and receives all the blood after a meal from the stomach and intestines via the portal vein. How does the body sense abundance in the environment?
Through the eyes? No... ye ol' LIVER...
If food (quantity and quality and composition) serves as one of the cues from our external physical environment, then the liver and the PPAR receptors located there there are the sensors of the degree of energy abundance/scarcity. What elements are essential for life outside of air? Food -- water -- light.... Similarly, what senses light? It is likely that VDR (vitamin D receptor) plays an equally important and parallel role. Abundant sunlight for most countries near the equator typically signals abundant food/energy. Vitamin D does rev up energy, productivity, and *hey* fertility! Naturally it follows that the skeletal muscles are the sensor for muscle movement and certainly the PPAR receptors in skeletal muscle do a great deal to command the balance of energy demand and supply/thermogenesis.
What might the holy trinity of human energy look like? mTOR--PPAR--VDR ? How might it have been shaped in our 'evolutionary heritage'...??? (thanks for the term Grey Whale!)
Well, we certainly know a lot of about what contribute's to this trinity's dysregulation...
Even statins improve this trinity... by activating (!!) PPAR ... This special anti-inflammatory and MMP-stabilizing effect occurs specifically at the macrophage level and for plaque, this translates directly to the surface, volume and core of plaque atheroma. The pleiotropic benefits of statins can now be attributed to a direct activation of PPAR on macrophages via the MAPK pathway.
Paumelle R, Staels B.Peroxisome proliferator-activated receptors mediate pleiotropic actions of statins.Circ Res. 2007 May 25;100(10):1394-5. No abstract available. (see Diagram: Cross-talk of statins/ PPARs in the antiatherogenic properties of statins --PDF here) PMID: 17525375
Yano M, Matsumura T, et al.Statins activate peroxisome proliferator-activated receptor gamma through extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase-dependent cyclooxygenase-2 expression in macrophages. Circ Res. 2007 May 25;100(10):1442-51. PMID: 17463321
Paumelle R, Staels B, et al.Acute antiinflammatory properties of statins involve peroxisome proliferator-activated receptor-alpha via inhibition of the protein kinase C signaling pathway.
Circ Res. 2006 Feb 17;98(3):361-9. PMID: 16397146
Landrier JF, Thomas C, et al.Statin induction of liver fatty acid-binding protein (L-FABP) gene expression is peroxisome proliferator-activated receptor-alpha-dependent.
J Biol Chem. 2004 Oct 29;279(44):45512-8. PMID: 15337740
Verreth W, De Keyzer D, et al.Rosuvastatin (INCREASES mRNA of PPAR-GAMMA AND) restores superoxide dismutase expression and inhibits accumulation of oxidized LDL in the aortic arch of obese dyslipidemic mice. Br J Pharmacol. 2007 Jun;151(3):347-55. PMID: 17384667
Roglans N, Sanguino E, et al.Atorvastatin treatment induced peroxisome proliferator-activated receptor alpha expression and decreased plasma nonesterified fatty acids and liver triglyceride in fructose-fed rats. J Pharmacol Exp Ther. 2002 Jul;302(1):232-9. PMID: 12065722
Sanguino E, Roglans N, et al.Atorvastatin reverses age-related reduction in rat hepatic PPARalpha and HNF-4. Br J Pharmacol. 2005 Aug;145(7):853-61. PMID: 15912134
In historical texts (ie, the Bible), the liver was actually considered 'the heart.' And, in the ancient days, harm to the liver was actually worse than to the heart. How were they so wise (without high tech ALT/AST tests or abdominal u/s) ??! For warriors, the liver was an easier, bigger target to hit than the smaller heart. We often neglect this fantastic vital organ. Interestingly, when the trinity is disrupted, this organ becomes metabolically deranged even before the heart.
Here are the liver's awesome functions and roles: