Poor Timing Of Fat Oxidation In Obesity Glucose Induced Fat Inhibition

More than a decade ago, the author's laboratory began to assess substrate competition in type 2 diabetes and obesity from the perspective of whether fat oxidation is appropriately regulated during fasting conditions. Using arteriovenous limb balance methods to assess oxygen and carbon dioxide exchange across the leg, we observed an elevated RQ across the leg after an overnight fast in type 2 DM (20), which denoted a decreased reliance on fat oxidation. Furthermore, there was reduced fractional extraction of fatty acids across the leg in type 2 DM (21). Experimentally, in lean, healthy volunteers, an increase in RQ across the leg was induced by hyperglycemia, even without elevation of insulin or marked suppression of plasma fatty acids; an even more pronounced effect was observed in obese, nondiabetic individuals (22). Thus, increased glucose availability was associated with depressed reliance on fat oxidation during fasting conditions. The elevated RQ response was associated with activation of pyruvate dehydrogenase (PDH) in muscle (22), the outer mitochondrial membrane enzyme complex controlling entry of glycolytic flux into the Krebs cycle for oxidation.

Thus, the pattern of glucose induced inhibition of fat oxidation in many respects is a mirror image of the opposite pattern of perturbations induced by elevating fatty acids, in which a blunting of the normal rise in RQ stimulated by insulin, and impaired activation of PDH are among key physiological alterations caused by elevated plasma fatty acids (9).

The Mediterranean Diet Meltdown

The Mediterranean Diet Meltdown

Looking To Lose Weight But Not Starve Yourself? Revealed! The Secret To Long Life And Good Health Is In The Foods We Eat. Download today To Discover The Reason Why The Mediterranean Diet Will Help You Have Great Health, Enjoy Life And Live Longer.

Get My Free Ebook


Post a comment