Peater Piper
Member
- Joined
- Mar 18, 2016
- Messages
- 817
Peat's obviously a big believer that healthy glucose metabolism should be favored over beta oxidation, and that many factors, including PUFA, excessive lypolysis, serotonin, estrogen, cortisol, lactate, and inflammation all steer the body away from oxidative metabolism, leading to even more derangements of metabolism. His focus often seems to be on how oxidative metabolism breaks down, but I haven't seen him pay much attention to how beta oxidation can become impaired.
This first study is about how glutathione depletion in elderly mice results in lower fasted mitochondrial NEFA oxidation, resulting in insulin resistance. Restoring glutathione levels increases NEFA oxidation and improves insulin sensitivity.
Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione. - PubMed - NCBI
This study tested subjects with no family history of type 2 diabetes, along with subjects with a family history of type 2 diabetes. They were either given a high fat or high carbohydrate meal. Both groups were age and fatness matched. With the high fat meal, the subjects with a family history of type 2 diabetes showed an inability to increase fatty acid oxidation in response to the lipid overload. This suggests a genetic component in some type 2 diabetics that limits their metabolic flexibility, which precedes insulin resistance.
Impaired Fat Oxidation After a Single High-Fat Meal in Insulin-Sensitive Nondiabetic Individuals With a Family History of Type 2 Diabetes | Diabetes
I looked up some Peat friendly substances and their effects on beta oxidation. Everyone here knows the benefits of glycine. It lowers cortisol, balances methionine, decreases inflammation, improves insulin sensitivity, etc. In this study, rats were fed sucrose heavy diets to increase NEFA, fat cell size, intra-abdominal fat accumulation, and blood pressure. Supplementing their water with 1% glycine caused a reduction in all values. "Mitochondrial respiration, as an indicator of the rate of fat oxidation, showed an increase in the state IV oxidation rate of the beta-oxidation substrates octanoic acid and palmitoyl carnitine. This suggests an enhancement of hepatic fatty acid metabolism, i.e., in their transport, activation, or beta-oxidation. These findings imply that the protection by glycine against elevated BP might be attributed to its effect in increasing fatty acid oxidation, reducing intra-abdominal fat accumulation and circulating NEFA, which have been proposed as links between obesity and hypertension."
Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed rats. - PubMed - NCBI
Next, taurine's potential role in beta oxidation. This paper hypothesizes that taurine forms a buffer in the mitochondrial matrix, allowing enzymes to function optimally. "Three acyl-CoA dehydrogenase enzymes, which are pivotal for beta-oxidation of fatty acids, are demonstrated to have optimal activity in a taurine buffer. By application of the model presented, taurine depletion caused by hyperglycemia could provide a link between mitochondrial dysfunction and diabetes."
A role for taurine in mitochondrial function
Caffeine and coffee (including decaf) are known to increase lipid metabolism in vivo. Peat's talked about coffee's ability to increase and support glucose oxidation. I haven't found any direct mechanisms for that, but it does increase hepatic beta oxidation through autophagy, which could be one of the (many) reasons habitual coffee drinkers seem to have improved glucose sensitivity compared to coffee abstainers.
Caffeine stimulates hepatic lipid metabolism by the autophagy-lysosomal pathway in mice - Sinha - 2014 - Hepatology - Wiley Online Library
Coffee induces autophagy in vivo. - PubMed - NCBI
Just to potentially contradict all of the above, especially the one showing an inability for diabetic relatives to switch to oxidative metabolism after a meal, this study falls a bit more in line with Peat's thinking. Excessive beta oxidation and an inability to switch to oxidative metabolism in a fasted-to-fed state leads to insulin resistance. Take beta oxidation out of the equation and insulin resistance doesn't occur. "In mice lacking malonyl-CoA decarboxylase (MCD), an enzyme that promotes mitochondrial β-oxidation by relieving malonyl-CoA-mediated inhibition of carnitine palmitoyltransferase 1. Thus, mcd−/−mice exhibit reduced rates of fat catabolism and resist diet-induced glucose intolerance despite high intramuscular levels of long-chain acyl-CoAs. These findings reveal a strong connection between skeletal muscle insulin resistance and lipid-induced mitochondrial stress."
http://www.sciencedirect.com/science/article/pii/S1550413107003063
So we have some evidence that impaired beta oxidation can result in insulin resistance, but in the obese, excessive lypolysis and beta oxidation can also impair glucose metabolism. In both cases, hyperglycemia occurs, but for different reasons. Substances like glycine and taurine, which work through a number of mechanisms, may actually work in both scenarios by reducing lypolysis through lowering cortisol and inflammation, while supporting complete beta oxidation.
Does this look right, or am I making a wrong turn somewhere?
This first study is about how glutathione depletion in elderly mice results in lower fasted mitochondrial NEFA oxidation, resulting in insulin resistance. Restoring glutathione levels increases NEFA oxidation and improves insulin sensitivity.
Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione. - PubMed - NCBI
This study tested subjects with no family history of type 2 diabetes, along with subjects with a family history of type 2 diabetes. They were either given a high fat or high carbohydrate meal. Both groups were age and fatness matched. With the high fat meal, the subjects with a family history of type 2 diabetes showed an inability to increase fatty acid oxidation in response to the lipid overload. This suggests a genetic component in some type 2 diabetics that limits their metabolic flexibility, which precedes insulin resistance.
Impaired Fat Oxidation After a Single High-Fat Meal in Insulin-Sensitive Nondiabetic Individuals With a Family History of Type 2 Diabetes | Diabetes
I looked up some Peat friendly substances and their effects on beta oxidation. Everyone here knows the benefits of glycine. It lowers cortisol, balances methionine, decreases inflammation, improves insulin sensitivity, etc. In this study, rats were fed sucrose heavy diets to increase NEFA, fat cell size, intra-abdominal fat accumulation, and blood pressure. Supplementing their water with 1% glycine caused a reduction in all values. "Mitochondrial respiration, as an indicator of the rate of fat oxidation, showed an increase in the state IV oxidation rate of the beta-oxidation substrates octanoic acid and palmitoyl carnitine. This suggests an enhancement of hepatic fatty acid metabolism, i.e., in their transport, activation, or beta-oxidation. These findings imply that the protection by glycine against elevated BP might be attributed to its effect in increasing fatty acid oxidation, reducing intra-abdominal fat accumulation and circulating NEFA, which have been proposed as links between obesity and hypertension."
Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed rats. - PubMed - NCBI
Next, taurine's potential role in beta oxidation. This paper hypothesizes that taurine forms a buffer in the mitochondrial matrix, allowing enzymes to function optimally. "Three acyl-CoA dehydrogenase enzymes, which are pivotal for beta-oxidation of fatty acids, are demonstrated to have optimal activity in a taurine buffer. By application of the model presented, taurine depletion caused by hyperglycemia could provide a link between mitochondrial dysfunction and diabetes."
A role for taurine in mitochondrial function
Caffeine and coffee (including decaf) are known to increase lipid metabolism in vivo. Peat's talked about coffee's ability to increase and support glucose oxidation. I haven't found any direct mechanisms for that, but it does increase hepatic beta oxidation through autophagy, which could be one of the (many) reasons habitual coffee drinkers seem to have improved glucose sensitivity compared to coffee abstainers.
Caffeine stimulates hepatic lipid metabolism by the autophagy-lysosomal pathway in mice - Sinha - 2014 - Hepatology - Wiley Online Library
Coffee induces autophagy in vivo. - PubMed - NCBI
Just to potentially contradict all of the above, especially the one showing an inability for diabetic relatives to switch to oxidative metabolism after a meal, this study falls a bit more in line with Peat's thinking. Excessive beta oxidation and an inability to switch to oxidative metabolism in a fasted-to-fed state leads to insulin resistance. Take beta oxidation out of the equation and insulin resistance doesn't occur. "In mice lacking malonyl-CoA decarboxylase (MCD), an enzyme that promotes mitochondrial β-oxidation by relieving malonyl-CoA-mediated inhibition of carnitine palmitoyltransferase 1. Thus, mcd−/−mice exhibit reduced rates of fat catabolism and resist diet-induced glucose intolerance despite high intramuscular levels of long-chain acyl-CoAs. These findings reveal a strong connection between skeletal muscle insulin resistance and lipid-induced mitochondrial stress."
http://www.sciencedirect.com/science/article/pii/S1550413107003063
So we have some evidence that impaired beta oxidation can result in insulin resistance, but in the obese, excessive lypolysis and beta oxidation can also impair glucose metabolism. In both cases, hyperglycemia occurs, but for different reasons. Substances like glycine and taurine, which work through a number of mechanisms, may actually work in both scenarios by reducing lypolysis through lowering cortisol and inflammation, while supporting complete beta oxidation.
Does this look right, or am I making a wrong turn somewhere?
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