Palmitic Acid (palmitate) Strongly Increases Oxidative Metabolism

[Mitchell777]

This is yet another thread as a follow up on the recent posts about plamitic acid inhibiting fatty acid oxidation and having therapeutic roles in cancer, diabetes and all other disease characterized by elevated/abnormal fatty acid metabolism.
Palmitic Acid (palmitate) Is A Fatty Acid Oxidation Inhibitor More Powerful Than Mildronate
Palmitic Acid (palmitate) Dramatically Inhibits Liver Cancer Progression

The study below shows that a physiological concentration (HED: ~3g) of palmitate basically doubled oxygen consumption/metabolism. The increase in respiration was NOT due to palmitate serving as the fuel, and fatty acid oxidation was not increased by palmitate either (something also suggested by the other threads on FAO inhibition).

Palmitate-induced activation of mitochondrial metabolism promotes oxidative stress and apoptosis in H4IIEC3 rat hepatocytes. - PubMed - NCBI
http://vanderbilt.edu/younglab/pdf/egnatchik14.pdf

"...ROS can be produced due to accelerated flux of electrons through the ETC as a result of increased mitochondrial activity. We measured the oxygen consumption of H4IIEC3 cells treated with 400 μmol/L PA to determine if ROS accumulation was associated with elevated mitochondrial metabolism. PA-treated cells were characterized by increased oxygen consumption (Fig. 2). Cells treated with 400 μmol/L OA had similar oxygen consumption rates as vehicle-treated cells. This result confirms that the elevated oxidative phenotype is unique to cells treated with SFA and that an equal load of MUFA is not sufficient to alter mitochondrial function."

"...Therefore, we analyzed ion fragments of citrate and malate for enrichment of M + 2 mass isotopomers (Fig. 6A). However, we found little to no incorporation of 13C, suggesting that a negligible flux of palmitate carbon was directed into the CAC for complete oxidation."

"...For example, ROS accumulation is a critical event leading to apoptosis of palmitate-treated CHO cells [30], while palmitate-treated neonatal cardiomyocytes undergo apoptosis independently of oxidative stress [31]. In our experiments, we measured a burst of ROS at approximately 6 h following palmitate administration, which was 25%–50% higher than cells treated with vehicle (BSA) alone."

"...Since mitochondria require oxygen to carry out oxidative phosphorylation, increased oxygen consumption is a direct measure of increased mitochondrial metabolism. Palmitate-treated cells exhibited a 2-fold increase in oxygen consumption rate and in most mitochondrial fluxes prior to ROS accumulation. However, NAC co-treatment did not affect palmitate-induced metabolic alterations, indicating that neither elevated ROS nor downstream apoptotic events contributed to mitochondrial activation. Instead, elevated mitochondrial metabolism appears to be an inherent consequence of palmitate overload that is independent of subsequent ROS accumulation and apoptosis initiation."

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What do you think of Stearic Acid compared to Palmitic Acid? What’s your thoughts on the comments below about Stearic acid.

“Dietary stearic acid is bareley even oxidized (burned in the mitochondria). In fact, stearic acid is the slowest to be burned at every level. When you eat fat, it is packed into chylomicrons by the intestine, from which it s released as free fatty acids which are taken up by cells through the transporter CD36 and ultimately transferred into the mitochondria by an enzyme called CPT1a, whose expression is controlled by PPAR alpha.”

“At literally every step in the pathway of fat oxidation, stearic acid is the slowpoke. Stearic acid is putting the brakes on the flood of fat into mitochondria to allow them to keep up. In contrast, oleic acid – which stearic acid is rapidly converted to by the enzyme SCD1 – is a racehorse. Is it any wonder that hibernating animals ramp up SCD1 expression to help them get torpid?9 Or that there is a direct correlation in humans between SCD1 expression in adipose tissue and fat mass?”

“What does all of this slowing down of fat flow by stearic acid add up to? A 2021 paper showed the effects of stearic acid on postprandial FFA levels. One of the main jobs of insulin is to suppress lipolysis to lower postprandial FFA levels. This prioritizes the burning of glucose to prevent blood glucose spikes. If you are eating a mixed diet, you WANT to suppress FFA after a meal. Compared to palmitic acid, stearic acid dramatically lowers postprandial FFA, especially after consecutive meals.”