Impact of Dietary Palmitic Acid on Lipid Metabolism

Abstract

Palmitic acid (PA) is ubiquitously present in dietary fat guaranteeing an average intake of about 20 g/d. The relative high requirement and relative content in the human body, which accounts for 20-30% of total fatty acids (FAs), is justified by its relevant nutritional role. In particular physiological conditions, such as in the fetal stage or in the developing brain, the respectively inefficient placental and brain blood-barrier transfer of PA strongly induces its endogenous biosynthesis from glucose via de novo lipogenesis (DNL) to secure a tight homeostatic control of PA tissue concentration required to exert its multiple physiological activities. However, pathophysiological conditions (insulin resistance) are characterized by a sustained DNL in the liver and aimed at preventing the excess accumulation of glucose, which result in increased tissue content of PA and disrupted homeostatic control of its tissue concentration. This leads to an overaccumulation of tissue PA, which results in dyslipidemia, increased ectopic fat accumulation, and inflammatory tone via toll-like receptor 4. Any change in dietary saturated FAs (SFAs) usually reflects a complementary change in polyunsaturated FA (PUFA) intake. Since PUFA particularly n-3 highly PUFA, suppress lipogenic gene expression, their reduction in intake rather than excess of dietary SFA may promote endogenous PA production via DNL. Thereby, the increase in tissue PA and its deleterious consequences from dysregulated DNL can be mistakenly attributed to dietary intake of PA.

Keywords: de novo lipogenesis; dietary fatty acids; fatty acid metabolism; palmitic acid; saturated/unsaturated ratio.

Figure 1

Combined consequences of liver insulin resistance and reduced PUFA intake. Insulin resistance in the liver is characterized by hyperinsulinemia and a reduced ability to store glycogen. In the presence of excess glucose, CHREBP is activated which, in turn, together with hyperinsulinemia, induces SREBP1c, and synergistically induces DNL (124) and thereby the biosynthesis of endogenous PA. Reduced PUFA intake can further promote PA and cholesterol biosynthesis since PUFAs inhibit both SREBP1c (123) and SREBP2 (125). Enhanced DNL can cause fatty liver and formation and release of VLDL enriched with PA and cholesterol esters. As a result, the accumulation of ectopic fat occurs in different tissues, and the increase in tissue PA can sustain insulin resistance by inducing inflammation through the activation of TLR4 (105) and accumulation of ceramides (106), setting in motion a vicious circle. Because reduced PUFA intake is often associated with an unbalanced increase in dietary SFA/PUFA, the rise in tissue PA can be mistakenly attributed to its dietary intake. CHREBP, carbohydrate-responsive element-binding protein; SREBP, sterol regulatory element-binding protein; DNL, de novo lipogenesis; PA, palmitic acid; PUFA, polyunsaturated fatty acid; TLR4, toll-like receptor 4; SFA, saturated fatty acid.