Send Your Metabolism The Right Signal With SEA

Did you know that your body fat composition is a signal to your metabolism? Should you be fattening up for winter? Do you live in a land of eternal summer?

Your body turns fat into ethanolamides which act as signaling molecules. Arachidonic acid as a signalling molecule is called AEA (arachidonoylethanolamide). AEA is an endocannabinoid, triggering your cannabinoid receptors and “giving you the munchies”. When oleic acid acts a a signal it is called OEA (oleoylethanolamide). OEA activates PPAR alpha and can contribute to the initiation of torpor.

Stearic acid as a signaling molecule (SEA) acts to help break down AEA and OEA by activating FAAH, the enzyme that degrades them. (Kasatkina, 2020) I pointed out in The History of Bodyfat Composition that stearic acid has declined precipitously and uniquely among fats over the last 80 years.  I present evidence in this video that this may have led to a corollary drop in circulating SEA levels.

You have too much OEA and AEA and not enough SEA!

SEA as a supplement reduces appetite and lowers SCD1 levels (Terrazzino, 2004), lowers inflammation (Berdyshev, 2015) and decreases circulating endocannabinoids. (Kasatkina, 2020)

Here is a thread of people’s experiences with SEA on r/SaturatedFat.

Astarita, G., Jung, K.-M., Vasilevko, V., DiPatrizio, N. V., Martin, S. K., Cribbs, D. H., Head, E., Cotman, C. W., & Piomelli, D. (2011). Elevated Stearoyl-CoA Desaturase in Brains of Patients with Alzheimer’s Disease. In S. Gaetani (Ed.), PLoS ONE (Vol. 6, Issue 10, p. e24777). Public Library of Science (PLoS).

Azar, S., Sherf-Dagan, S., Nemirovski, A., Webb, M., Raziel, A., Keidar, A., Goitein, D., Sakran, N., Shibolet, O., Tam, J., & Zelber-Sagi, S. (2018). Circulating Endocannabinoids Are Reduced Following Bariatric Surgery and Associated with Improved Metabolic Homeostasis in Humans. In Obesity Surgery (Vol. 29, Issue 1, pp. 268–276). Springer Science and Business Media LLC.

Balsevich, G., Sticht, M., Bowles, N. P., Singh, A., Lee, T. T. Y., Li, Z., Chelikani, P. K., Lee, F. S., Borgland, S. L., Hillard, C. J., McEwen, B. S., & Hill, M. N. (2018). Role for fatty acid amide hydrolase (FAAH) in the leptin-mediated effects on feeding and energy balance. In Proceedings of the National Academy of Sciences (Vol. 115, Issue 29, pp. 7605–7610). Proceedings of the National Academy of Sciences.

Berdyshev, A. G., Kosiakova, H. V., Onopchenko, O. V., Panchuk, R. R., Stoika, R. S., & Hula, N. M. (2015). N-Stearoylethanolamine suppresses the pro-inflammatory cytokines production by inhibition of NF-κB translocation. In Prostaglandins & Other Lipid Mediators (Vol. 121, pp. 91–96). Elsevier BV.

Biddinger, S. B., Miyazaki, M., Boucher, J., Ntambi, J. M., & Kahn, C. R. (2006). Leptin Suppresses Stearoyl-CoA Desaturase 1 by Mechanisms Independent of Insulin and Sterol Regulatory Element–Binding Protein-1c. In Diabetes (Vol. 55, Issue 7, pp. 2032–2041). American Diabetes Association.

Bruun, S., Gouveia-Figueira, S., Domellöf, M., Husby, S., Neergaard Jacobsen, L., Michaelsen, K., Fowler, C., & Zachariassen, G. (2018). Satiety Factors Oleoylethanolamide, Stearoylethanolamide, and Palmitoylethanolamide in Mother’s Milk Are Strongly Associated with Infant Weight at Four Months of Age—Data from the Odense Child Cohort. In Nutrients (Vol. 10, Issue 11, p. 1747). MDPI AG.

Camacho‐Muñoz, D., Kiezel‐Tsugunova, M., Kiss, O., Uddin, M., Sundén, M., Ryaboshapkina, M., Lind, L., Oscarsson, J., & Nicolaou, A. (2021). Omega‐3 carboxylic acids and fenofibrate differentially alter plasma lipid mediators in patients with non‐alcoholic fatty liver disease. In The FASEB Journal (Vol. 35, Issue 11). Wiley.

Chao, P.-M., Huang, H.-L., Liao, C.-H., Huang, S.-T., & Huang, C. (2007). A high oxidised frying oil content diet is less adipogenic, but induces glucose intolerance in rodents. In British Journal of Nutrition (Vol. 98, Issue 1, pp. 63–71). Cambridge University Press (CUP).

Lisa P. Chu; Steven J. Swoap (2012). Oral bezafibrate induces daily torpor and FGF21 in mice in a PPAR alpha dependent manner. , 37(4), 0–296. doi:10.1016/j.jtherbio.2011.11.011

Dalle Carbonare, M., Del Giudice, E., Stecca, A., Colavito, D., Fabris, M., D’Arrigo, A., Bernardini, D., Dam, M., & Leon, A. (2008). A Saturated N-Acylethanolamine Other than N-Palmitoyl Ethanolamine with Anti-inflammatory Properties: a Neglected Story…. In Journal of Neuroendocrinology (Vol. 20, Issue s1, pp. 26–34). Wiley.

Dziuba, O. S., Hudz, Ie. A., & Kosiakova, H. V. (2018). The effect of N-stearoylethanolamine on adipocytes free cholesterol content and phospholipid composition in rats with obesity-induced insulin resistance. In The Ukrainian Biochemical Journal (Vol. 90, Issue 5, pp. 81–90). National Academy of Sciences of Ukraine (Co. LTD Ukrinformnauka) (Publications).

Fanelli, F., Mezzullo, M., Repaci, A., Belluomo, I., Ibarra Gasparini, D., Di Dalmazi, G., Mastroroberto, M., Vicennati, V., Gambineri, A., Morselli-Labate, A. M., Pasquali, R., & Pagotto, U. (2018). Profiling plasma N-Acylethanolamine levels and their ratios as a biomarker of obesity and dysmetabolism. In Molecular Metabolism (Vol. 14, pp. 82–94). Elsevier BV.

Joosten, M. M., Balvers, M. G., Verhoeckx, K. C., Hendriks, H. F., & Witkamp, R. F. (2010). Plasma anandamide and other N-acylethanolamines are correlated with their corresponding free fatty acid levels under both fasting and non-fasting conditions in women. In Nutrition & Metabolism (Vol. 7, Issue 1, p. 49). Springer Science and Business Media LLC.

Laleh, P., Yaser, K., Abolfazl, B., Shahriar, A., Mohammad, A. J., Nazila, F., & Alireza, O. (2018). Oleoylethanolamide increases the expression of PPAR-Α and reduces appetite and body weight in obese people: A clinical trial. In Appetite (Vol. 128, pp. 44–49). Elsevier BV.

Liu, J., Cinar, R., Xiong, K., Godlewski, G., Jourdan, T., Lin, Y., Ntambi, J. M., & Kunos, G. (2013). Monounsaturated fatty acids generated via stearoyl CoA desaturase-1 are endogenous inhibitors of fatty acid amide hydrolase. In Proceedings of the National Academy of Sciences (Vol. 110, Issue 47, pp. 18832–18837). Proceedings of the National Academy of Sciences.

Kasatkina, L. A., Heinemann, A., Hudz, Y. A., Thomas, D., & Sturm, E. M. (2020). Stearoylethanolamide interferes with retrograde endocannabinoid signalling and supports the blood-brain barrier integrity under acute systemic inflammation. In Biochemical Pharmacology (Vol. 174, p. 113783). Elsevier BV.

Nirengi, S., Homma, T., Inoue, N., Sato, H., Yoneshiro, T., Matsushita, M., Kameya, T., Sugie, H., Tsuzaki, K., Saito, M., Sakane, N., Kurosawa, Y., & Hamaoka, T. (2016). Assessment of human brown adipose tissue density during daily ingestion of thermogenic capsinoids using near-infrared time-resolved spectroscopy. In Journal of Biomedical Optics (Vol. 21, Issue 9, p. 091305). SPIE-Intl Soc Optical Eng.

Onopchenko, O. V., Kosiakova, G. V., Oz, M., Klimashevsky, V. M., & Gula, N. M. (2014). N-Stearoylethanolamine Restores Pancreas Lipid Composition in Obesity-Induced Insulin Resistant Rats. In Lipids (Vol. 50, Issue 1, pp. 13–21). Wiley.

Reeves, Valerie L.. “A diet enriched in stearic acid protects against the progression of type 2 diabetes in leptin receptor deficient mice (db/db).” (2012).

Rivilla, V. M., Jiménez-Serra, I., Martín-Pintado, J., Briones, C., Rodríguez-Almeida, L. F., Rico-Villas, F., Tercero, B., Zeng, S., Colzi, L., de Vicente, P., Martín, S., & Requena-Torres, M. A. (2021). Discovery in space of ethanolamine, the simplest phospholipid head group. In Proceedings of the National Academy of Sciences (Vol. 118, Issue 22). Proceedings of the National Academy of Sciences.

Terrazzino, S., Berto, F., Carbonare, M. D., Fabris, M., Guiotto, A., Bernardini, D., & Leon, A. (2004). Stearoylethanolamide exerts anorexic effects in mice via downregulation of liver stearoyl‐coenzyme A desaturase‐1 mRNA expression. In The FASEB Journal (Vol. 18, Issue 13, pp. 1580–1582). Wiley.

Tutunchi, H., Ostadrahimi, A., Saghafi‐Asl, M., & Maleki, V. (2019). The effects of oleoylethanolamide, an endogenous PPAR‐α agonist, on risk factors for NAFLD: A systematic review. In Obesity Reviews (Vol. 20, Issue 7, pp. 1057–1069). Wiley.

Zhang, L. L., Yan Liu, D., Ma, L. Q., Luo, Z. D., Cao, T. B., Zhong, J., Yan, Z. C., Wang, L. J., Zhao, Z. G., Zhu, S. J., Schrader, M., Thilo, F., Zhu, Z. M., & Tepel, M. (2007). Activation of Transient Receptor Potential Vanilloid Type-1 Channel Prevents Adipogenesis and Obesity. In Circulation Research (Vol. 100, Issue 7, pp. 1063–1070). Ovid Technologies (Wolters Kluwer Health).