Palmitic Acid: Physiological Role, Metabolism and Nutritional Implications

Abstract

Palmitic acid (PA) has been for long time negatively depicted for its putative detrimental health effects, shadowing its multiple crucial physiological activities. PA is the most common saturated fatty acid accounting for 20-30% of total fatty acids in the human body and can be provided in the diet or synthesized endogenously via de novo lipogenesis (DNL). PA tissue content seems to be controlled around a well-defined concentration, and changes in its intake do not influence significantly its tissue concentration because the exogenous source is counterbalanced by PA endogenous biosynthesis. Particular physiopathological conditions and nutritional factors may strongly induce DNL, resulting in increased tissue content of PA and disrupted homeostatic control of its tissue concentration. The tight homeostatic control of PA tissue concentration is likely related to its fundamental physiological role to guarantee membrane physical properties but also to consent protein palmitoylation, palmitoylethanolamide (PEA) biosynthesis, and in the lung an efficient surfactant activity. In order to maintain membrane phospholipids (PL) balance may be crucial an optimal intake of PA in a certain ratio with unsaturated fatty acids, especially PUFAs of both n-6 and n-3 families. However, in presence of other factors such as positive energy balance, excessive intake of carbohydrates (in particular mono and disaccharides), and a sedentary lifestyle, the mechanisms to maintain a steady state of PA concentration may be disrupted leading to an over accumulation of tissue PA resulting in dyslipidemia, hyperglycemia, increased ectopic fat accumulation and increased inflammatory tone via toll-like receptor 4. It is therefore likely that the controversial data on the association of dietary PA with detrimental health effects, may be related to an excessive imbalance of dietary PA/PUFA ratio which, in certain physiopathological conditions, and in presence of an enhanced DNL, may further accelerate these deleterious effects.

Keywords: de novo lipogenesis; lung surfactant; palmitic acid; palmitoylethanolamide; protein palmitoylation.

Figure 1

Interplay between CD 36 and AMPK in modulating cellular metabolic pathways with adequate or excess dietary fat, in physiological and pathophysiological conditions. CD36 contributes, under excessive fat supply, to lipid accumulation and metabolic dysfunction signaling (Pepino et al., 2014) and might influence AMPK activation (Samovski et al., 2015). In presence of excess exogenous FA concentrations CD36 is diysfunctional and suppresses AMPK, and might contribute to the reported association of CD36 variants with metabolic complications of obesity in humans. Physiologically adequate CD36-FA interactions activates AMPK (Samovski et al., 2015) contributing to the maintenance of cellular fatty acids homeostasis. Pointing out on the importance of CD36 in cellular fatty acid homeostasis, CD36-deficient mice are resistant to alcohol- and high-carbohydrate-induced hepatic steatosis (Clugston et al., 2014). Therefore, CD36, in particular dysmetabolic conditions, by suppressing AMPK activation, may enhance DNL and thereby promote cancer cell proliferation. Indeed, it has been recently shown that cancer cells that express high levels of the fatty acid receptor CD36 and lipid metabolism genes, are unique in their ability to initiate metastasis in the presence of an excess of dietary fat (Pascual et al., 2017). Arrows in red depict metabolic dysfunction pathways, in blue physiological pathways. Abbreviations: FA, fatty acids; PPP, pentose-phosphate pathway.

Figure 2

Nutritional factors affecting tissue PA homeostatic balance, disruption of which leads to severe pathophysiological consequences.