Fat Metabolism in Context: PPAR alpha, Saturated Fat and NAD+

PPAR alpha is a nuclear receptor that is often said to be crucial for fat metabolism.  It increases the activity of enzymes that increase fat flow into mitochondria and increase beta oxidation: fat burning.

Having said that, the functions of PPAR alpha are largely redundant with PPAR delta, which is more highly expressed in most tissues.  PPAR alpha also has some “odd” activities, such as increasing lipogenic enzymes such as SCD1 and D6D.  This leads to making fat while burning fat.  A curious effect.

PPAR alpha is activated by the oleic acid in olive oil and the lauric acid in cocnut oil.  In this video I argue that the CONTEXT within which you activate PPAR alpha is of crucial importance.  Saturated fat leads to high NAD+ levels leads to PPAR alpha activating fat burning. Unsaturated fat leads to low NAD+ levels leads to PPAR activating fat making.

Braissant, O., Foufelle, F., Scotto, C., Dauça, M., & Wahli, W. (1996). Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. In Endocrinology (Vol. 137, Issue 1, pp. 354–366). The Endocrine Society. https://doi.org/10.1210/endo.137.1.8536636

Dominy, J. E., Gerhart-Hines, Z., & Puigserver, P. (2011). Nutrient-Dependent Acetylation Controls Basic Regulatory Metabolic Switches and Cellular Reprogramming. In Cold Spring Harbor Symposia on Quantitative Biology (Vol. 76, Issue 0, pp. 203–209). Cold Spring Harbor Laboratory. https://doi.org/10.1101/sqb.2012.76.010843

Dragos, S. M., Bergeron, K. F., Desmarais, F., Suitor, K., Wright, D. C., Mounier, C., & Mutch, D. M. (2017). Reduced SCD1 activity alters markers of fatty acid reesterification, glyceroneogenesis, and lipolysis in murine white adipose tissue and 3T3-L1 adipocytes. In American Journal of Physiology-Cell Physiology (Vol. 313, Issue 3, pp. C295–C304). American Physiological Society. https://doi.org/10.1152/ajpcell.00097.2017

Haczeyni, F., Wang, H., Barn, V., Mridha, A. R., Yeh, M. M., Haigh, W. G., Ioannou, G. N., Choi, Y., McWherter, C. A., Teoh, N. C. ‐H., & Farrell, G. C. (2017). The selective peroxisome proliferator–activated receptor‐delta agonist seladelpar reverses nonalcoholic steatohepatitis pathology by abrogating lipotoxicity in diabetic obese mice. In Hepatology Communications (Vol. 1, Issue 7, pp. 663–674). Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.1002/hep4.1072

Human basal metabolic rate has declined over the past 30 years. (2023). In Nature Metabolism (Vol. 5, Issue 4, pp. 544–545). Springer Science and Business Media LLC. https://doi.org/10.1038/s42255-023-00790-2

Muoio, D. M., MacLean, P. S., Lang, D. B., Li, S., Houmard, J. A., Way, J. M., Winegar, D. A., Corton, J. C., Dohm, G. L., & Kraus, W. E. (2002). Fatty Acid Homeostasis and Induction of Lipid Regulatory Genes in Skeletal Muscles of Peroxisome Proliferator-activated Receptor (PPAR) α Knock-out Mice. In Journal of Biological Chemistry (Vol. 277, Issue 29, pp. 26089–26097). Elsevier BV. https://doi.org/10.1074/jbc.m203997200

Oosterveer, M. H., Grefhorst, A., van Dijk, T. H., Havinga, R., Staels, B., Kuipers, F., Groen, A. K., & Reijngoud, D.-J. (2009). Fenofibrate Simultaneously Induces Hepatic Fatty Acid Oxidation, Synthesis, and Elongation in Mice. In Journal of Biological Chemistry (Vol. 284, Issue 49, pp. 34036–34044). Elsevier BV. https://doi.org/10.1074/jbc.m109.051052

Petrus, P., Edholm, D., Rosqvist, F., Dahlman, I., Sundbom, M., Arner, P., Rydén, M., & Risérus, U. (2017). Depot-specific differences in fatty acid composition and distinct associations with lipogenic gene expression in abdominal adipose tissue of obese women. In International Journal of Obesity (Vol. 41, Issue 8, pp. 1295–1298). Springer Science and Business Media LLC. https://doi.org/10.1038/ijo.2017.106

Powell, Maude. (1930). THE METABOLISM OF TRICAPRYLIN AND TRILAURIN. https://sci.bban.top/pdf/10.1016/s0021-9258%252818%252976693-3.pdf?download=true

Ortiz, M., Soto-Alarcón, S. A., Orellana, P., Espinosa, A., Campos, C., López-Arana, S., Rincón, M. A., Illesca, P., Valenzuela, R., & Videla, L. A. (2020). Suppression of high-fat diet-induced obesity-associated liver mitochondrial dysfunction by docosahexaenoic acid and hydroxytyrosol co-administration. In Digestive and Liver Disease (Vol. 52, Issue 8, pp. 895–904). Elsevier BV. https://doi.org/10.1016/j.dld.2020.04.019

Oscarsson, J., Önnerhag, K., Risérus, U., Sundén, M., Johansson, L., Jansson, P.-A., Moris, L., Nilsson, P. M., Eriksson, J. W., & Lind, L. (2018). Effects of free omega-3 carboxylic acids and fenofibrate on liver fat content in patients with hypertriglyceridemia and non-alcoholic fatty liver disease: A double-blind, randomized, placebo-controlled study. In Journal of Clinical Lipidology (Vol. 12, Issue 6, pp. 1390-1403.e4). Elsevier BV. https://doi.org/10.1016/j.jacl.2018.08.003

Pettinelli, P., del Pozo, T., Araya, J., Rodrigo, R., Araya, A. V., Smok, G., Csendes, A., Gutierrez, L., Rojas, J., Korn, O., Maluenda, F., Diaz, J. C., Rencoret, G., Braghetto, I., Castillo, J., Poniachik, J., & Videla, L. A. (2009). Enhancement in liver SREBP-1c/PPAR-α ratio and steatosis in obese patients: Correlations with insulin resistance and n-3 long-chain polyunsaturated fatty acid depletion. In Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease (Vol. 1792, Issue 11, pp. 1080–1086). Elsevier BV. https://doi.org/10.1016/j.bbadis.2009.08.015

Pontis, S., Ribeiro, A., Sasso, O., & Piomelli, D. (2015). Macrophage-derived lipid agonists of PPAR-αas intrinsic controllers of inflammation. In Critical Reviews in Biochemistry and Molecular Biology (Vol. 51, Issue 1, pp. 7–14). Informa UK Limited. https://doi.org/10.3109/10409238.2015.1092944

Risérus, U., Sprecher, D., Johnson, T., Olson, E., Hirschberg, S., Liu, A., Fang, Z., Hegde, P., Richards, D., Sarov-Blat, L., Strum, J. C., Basu, S., Cheeseman, J., Fielding, B. A., Humphreys, S. M., Danoff, T., Moore, N. R., Murgatroyd, P., O’Rahilly, S., … Karpe, F. (2008). Activation of Peroxisome Proliferator–Activated Receptor (PPAR)δ Promotes Reversal of Multiple Metabolic Abnormalities, Reduces Oxidative Stress, and Increases Fatty Acid Oxidation in Moderately Obese Men. In Diabetes (Vol. 57, Issue 2, pp. 332–339). American Diabetes Association. https://doi.org/10.2337/db07-1318

Thomas, M., Burk, O., Klumpp, B., Kandel, B. A., Damm, G., Weiss, T. S., Klein, K., Schwab, M., & Zanger, U. M. (2013). Direct Transcriptional Regulation of Human Hepatic Cytochrome P450 3A4 (CYP3A4) by Peroxisome Proliferator–Activated Receptor Alpha (PPARα). In Molecular Pharmacology (Vol. 83, Issue 3, pp. 709–718). American Society for Pharmacology & Experimental Therapeutics (ASPET). https://doi.org/10.1124/mol.112.082503

Xia, J., Yu, P., Zeng, Z., Ma, M., Zhang, G., Wan, D., Gong, D., Deng, S., & Wang, J. (2021). Lauric Triglyceride Ameliorates High-Fat-Diet-Induced Obesity in Rats by Reducing Lipogenesis and Increasing Lipolysis and β-Oxidation. In Journal of Agricultural and Food Chemistry (Vol. 69, Issue 32, pp. 9157–9166). American Chemical Society (ACS). https://doi.org/10.1021/acs.jafc.0c07342

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