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Review
. 2022 Jul 8;11(14):2146.
doi: 10.3390/cells11142146.

Roles of Palmitoleic Acid and Its Positional Isomers, Hypogeic and Sapienic Acids, in Inflammation, Metabolic Diseases and Cancer

Miguel A Bermúdez  1   2 , Laura Pereira  1   2 , Cristina Fraile  1 , Laura Valerio  1 , María A Balboa  1   2 , Jesús Balsinde  1   2
Affiliations
Review

Roles of Palmitoleic Acid and Its Positional Isomers, Hypogeic and Sapienic Acids, in Inflammation, Metabolic Diseases and Cancer

Miguel A Bermúdez et al. Cells. .

Abstract

In the last few years, the monounsaturated hexadecenoic fatty acids are being increasingly considered as biomarkers of health with key functions in physiology and pathophysiology. Palmitoleic acid (16:1n-7) and sapienic acid (16:1n-10) are synthesized from palmitic acid by the action of stearoyl-CoA desaturase-1 and fatty acid desaturase 2, respectively. A third positional isomer, hypogeic acid (16:1n-9) is produced from the partial β-oxidation of oleic acid. In this review, we discuss the current knowledge of the effects of palmitoleic acid and, where available, sapienic acid and hypogeic acid, on metabolic diseases such as diabetes, cardiovascular disease, and nonalcoholic fatty liver disease, and cancer. The results have shown diverse effects among studies in cell lines, animal models and humans. Palmitoleic acid was described as a lipokine able to regulate different metabolic processes such as an increase in insulin sensitivity in muscle, β cell proliferation, prevention of endoplasmic reticulum stress and lipogenic activity in white adipocytes. Numerous beneficial effects have been attributed to palmitoleic acid, both in mouse models and in cell lines. However, its role in humans is not fully understood, and is sometimes controversial. Regarding sapienic acid and hypogeic acid, studies on their biological effects are still scarce, but accumulating evidence suggests that they also play important roles in metabolic regulation. The multiplicity of effects reported for palmitoleic acid and the compartmentalized manner in which they often occur, may suggest the overlapping actions of multiple isomers being present at the same or neighboring locations.

Keywords: cardiovascular disease; diabetes and obesity; hexadecenoic fatty acid; lipid compartmentalization; lipid signaling; liver disease.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Pathways of biosynthesis of hexadecenoic fatty acids. Palmitoleic acid (16:1n-7) is synthesized in the endoplasmic reticulum via desaturation of palmitic acid (16:0) at C9 via SCD. Hypogeic acid (16:1n-9) is synthesized in the mitochondria via β-oxidation of oleic acid (18:1n-1). Sapienic acid (16:1n-10) is synthesized in the mitochondria and endoplasmic reticulum via desaturation of 16:0 at C6 via FADS2.
Figure 2
Figure 2
Summary of the effects of 16:1n-7 on metabolic and inflammatory conditions in obesity and diabetes.
Figure 3
Figure 3
Summary of effects of 16:1n-7 on metabolic and inflammatory conditions in cardiovascular disease and atherosclerosis.
Figure 4
Figure 4
Phospholipase A2-mediated signaling in activated macrophages. The macrophages utilize two cytosolic phospholipase A2s of similar size but with clearly differentiated functions, to effect lipid signaling leading to either pro- or anti-inflammatory actions. On the one hand, group IVA calcium-dependent phospholipase A2 (cPLA2α) releases arachidonic acid (AA) from membrane phospholipids, giving rise to the formation of pro-inflammatory eicosanoids. On the other hand, group VIA calcium-independent phospholipase A2 (iPLA2β) controls the metabolism of hexadecenoic fatty acids (palmitoleic acid, hypogeic acid, and sapienic acid), thus regulating new lipid metabolic pathways with anti-inflammatory character. The abbreviation PL(FA/AA) represents any given phospholipid (PL) containing an unspecified fatty acid (FA) at the sn-1 position, and arachidonic acid (AA) at the sn-2 position. PC(16:0/16:1), 1-palmitoyl-2-hexadecenoyl-sn-glycero-3-phosphocholine; PI(18:0/16:1), 1-stearoyl-2-hexadecenoyl-sn-glycero-3-phospho-inositol; FAHFA, branched fatty acyl esters of hydroxy fatty acids.
Figure 5
Figure 5
Summary of effects of hexadecenoic fatty acids in liver diseases (left) and cancer (right).
See this image and copyright information in PMC

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