Diet-derived and diet-related endogenously produced palmitic acid: Effects on metabolic regulation and cardiovascular disease risk

• Published in: Journal of clinical lipidology 2023-09, Vol.17 (5), p.577-586
• Main Authors: Annevelink, Carmen E., Sapp, Philip A., Petersen, Kristina S., Shearer, Greg C., Kris-Etherton, Penny M.
• Format: Article
• Language: English
• Subjects: Carbohydrates; Cardiovascular Diseases - etiology; Ceramides; CVD risk; Diet, Fat-Restricted; Diet-derived; Dietary Fats - metabolism; Endogenous synthesis; FAHFAs; Fatty Acids; Humans; Obesity - metabolism; Overweight; Palmitic Acid
• ISSN: 1933-2874; 1876-4789
• DOI: 10.1016/j.jacl.2023.07.005

•Plasma palmitic acid is derived from dietary fat and also from de novo lipogenesis (DNL) and lipolysis.•A low-fat diet promotes palmitic acid synthesis and a high-fat diet provides palmitic acid from food.•Palmitic acid increases CVD risk by raising LDL-C, synthesis of ceramides and branched fatty acid esters of hydroxy fatty acids (FAHFAs) derived from palmitic acid. Palmitic acid is the predominant dietary saturated fatty acid (SFA) in the US diet. Plasma palmitic acid is derived from dietary fat and also endogenously from de novo lipogenesis (DNL) and lipolysis. DNL is affected by excess energy intake resulting in overweight and obesity, and the macronutrient profile of the diet. A low-fat diet (higher carbohydrate and/or protein) promotes palmitic acid synthesis in adipocytes and the liver. A high-fat diet is another source of palmitic acid that is taken up by adipose tissue, liver, heart and skeletal muscle via lipolytic mechanisms. Moreover, overweight/obesity and accompanying insulin resistance increase non-esterified fatty acid (NEFA) production. Palmitic acid may affect cardiovascular disease (CVD) risk via mechanisms beyond increasing LDL-C, notably synthesis of ceramides and possibly through branched fatty acid esters of hydroxy fatty acids (FAHFAs) from palmitic acid. Ceramides are positively associated with incident CVD, whereas the role of FAHFAs is uncertain. Given the new evidence about dietary regulation of palmitic acid metabolism there is interest in learning more about how diet modulates circulating palmitic acid concentrations and, hence, potentially CVD risk. This is important because of the heightened interest in low carbohydrate (carbohydrate controlled) and high carbohydrate (low-fat) diets coupled with the ongoing overweight/obesity epidemic, all of which can increase plasma palmitic acid levels by different mechanisms. Consequently, learning more about palmitic acid biochemistry, trafficking and how its metabolites affect CVD risk will inform future dietary guidance to further lower the burden of CVD.