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Palmitoleic Acid

Palmitoleic Acid Molecule

Linear Formula



(9Z)-Hexadecenoic acid, cis-9-hexadecenoic acid, palmitoleate

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Palmitoleic acid, or cis-9-hexadecenoic acid, 16:1n-7, is an omega-7 monounsaturated fatty acid (MUFA). MUFAs are classified as fatty acids containing a single double bond. MUFA biosynthesis occurs through its rate-limiting enzyme stearoyl-CoA desaturase (SCD), with palmitoleic acid and oleic acid representing major MUFAs that significantly impact health and physiology. Although palmitoleic acid is present in all tissues, it is particularly enriched in the liver and adipose tissue. High concentrations of dietary fatty acids are also found in fish oil, macadamia oil, and sea buckthorn oil1.

MUFAs are critical for maintaining biological membrane fluidity and have gained considerable attention in research for their effects on human health2. Research has described palmitoleic acid as a “lipokine” that orchestrates metabolic responses between peripheral tissues and increased palmitoleic acid levels are generally associated with beneficial health outcomes. In contrast, saturated fatty acids such as palmitic acid are linked to detrimental health outcomes.

Palmitoleic acid and Metabolic health

Impairments in lipid metabolism and changes to free fatty acids are central to the development of metabolic disorders such as obesity and type 2 diabetes. Notably, palmitoleic acid has been shown to be particularly important in the regulation of glucose metabolism and as a signaling molecule (i.e., lipokine) between tissues and systemic metabolism.

For example, one study demonstrated that individuals with high baseline levels of circulating palmitoleic acid exhibit increased insulin sensitivity, suggesting that palmitoleic acid exerts protective effects against insulin resistance3. In support of these data, in vitro studies found that palmitoleic acid application on macrophages sensitizes insulin signaling in skeletal muscle myotubes, suggesting that palmitoleic acid acts as an important intermediary between skeletal muscle and the inflammatory immune responses that occurs in metabolic disorders4.

Further evidence for palmitoleic acid as a lipokine comes from animal studies. Increasing lipogenesis in fatty acid-binding protein-deficient mice significantly improved the systemic effects of high-fat diet exposure, a result attributed to adipose-derived palmitoleic acid acting on muscle insulin action and suppression of hepatic steatosis5.

Palmitoleic acid and Liver health

The aberrant increase in lipogenesis and fatty acids present in metabolic disorders is also a leading factor in the development of non-alcoholic liver diseases. Considering the beneficial effects of palmitoleic acid on glucose metabolism, recent research has also demonstrated that palmitoleic acid is protective against liver impairments induced by obesity development.

In one study, high-fat diet intake in mice significantly increased body weight and induced dyslipidemia and hepatic steatosis. Treatment with palmitoleic acid not only suppressed weight gain and lipid accumulation in the liver but also decreased the expression of genes associated with fatty acid uptake and obesity-related inflammation. Similarly, other studies demonstrated that palmitoleic acid supplementation in a mouse model of type 2 diabetes significantly reduced liver and hepatic triglyceride levels, accompanied by the downregulation of lipogenic genes in the liver7.

Palmitoleic acid and Cardiovascular Health

Atherosclerosis is a critical pathological process that underlies cardiovascular disease and is driven by impaired lipid metabolism and elevated inflammation. Researchers have also examined palmitoleic acid supplementation in mitigating the outcomes of cardiovascular diseases, considering its beneficial effects in metabolic disorders. Atherosclerosis is characterized by endothelial cell dysfunction triggered by dyslipidemia and inflammation. However, the anti-inflammatory effects of palmitoleic acid on endothelial cells are currently under investigation.

One in vitro study using cultured endothelial cells stimulated with proinflammatory cytokines demonstrated that the application of palmitoleic acid downregulated several proinflammatory genes. Interestingly, this study also showed that palmitoleic acid had greater anti-inflammatory properties compared to another dominant MUFA, oleic acid8.

In another study, LDL receptor knockout (LDLR-KO) mice fed a high-fat diet exhibited profound metabolic dysfunction and atherosclerosis. Palmitoleic acid supplementation improved several metabolic parameters, including a decrease in triglycerides, improved glucose metabolism, and a decrease in genes that regulate inflammatory cytokines. Notably, palmitoleic acid reduced atherosclerotic plaque area by ~45%9. Taken together, these data provide evidence for palmitoleic acid as a potential dietary factor that can prevent cardiovascular disease.

Palmitoleic acid and Gastrointestinal Health

Considering the effects of palmitoleic acid on metabolic health, it is unsurprising that emerging research has also implicated this metabolite in modulating gastrointestinal health and the gut microbiome. Serum levels of palmitoleic acid have been identified as a potential biomarker for inflammatory bowel disease (IBD)10 and several studies have shown that dietary sources of palmitoleic acid can reprogram gut microbiota to protect against deficits in gut health.

For instance, a study involving an IBD mouse model demonstrated that oral supplementation with palmitoleic acid repaired gut mucosal barriers and decreased the expression of proinflammatory cytokines. Furthermore, treatment with palmitoleic acid on cultured inflamed colon tissue from Crohn’s disease patients similarly reduced proinflammatory markers and repaired tissue. These effects were attributed to beneficial changes in gut microbiota, particularly a selective increase in the anti-inflammatory gut bacterium Akkermansia muciniphila. Interestingly, transfer of this bacterium in conjunction with palmitoleic acid treatment showed synergistic protection against colitis in mice11.

Palmitoleic acid and Oncology

Dysfunctions in lipid metabolism play a critical role in the development of cancer and considerable attention has been focused on examining modulations in fatty acid distribution as a possible biomarker for cancer prognosis. Importantly, accelerated lipogenesis occurs early in carcinogenesis, providing a promising intervention target for cancer prevention12. Recent studies examining cancer and lipid metabolism have identified changes in MUFA levels, including palmitoleic acid.

A report examining fatty acid composition in colorectal cancer tissue found 20-50% lower levels of palmitoleic acid, along with changes in levels of other fatty acid species13. Furthermore, in vitro experiments examining hepatoma cells revealed that conjugated linoleic acid has anti-carcinogenic properties, an effect that is reversed by the application of palmitoleic acid14. Collectively, these results suggest that the balance of fatty acid distribution and the modulation of palmitoleic acid may be a potential mechanism underlying cancer cell survivability.

Palmitoleic acid and Research

As of March 2024, there are over 1,600 citations for palmitoleic acid in research publications (excluding books and documents) on Pubmed. The large number of publications linking this metabolite to a broad range of physiological functions suggests that any research program seeking to better understand metabolic, liver, cardiovascular, gastrointestinal, and oncological health may benefit from quantitative analysis of palmitoleic acid. Considering the importance of palmitoleic acid in biological functions, preclinical research may also benefit from palmitoleic acid quantification to further the understanding of biomarkers, diagnosis, and disease monitoring.


  1. Wishart DS, Guo A, Oler E, et al. HMDB 5.0: the Human Metabolome Database for 2022. Nucleic Acids Res 2022;(50):D622-D631.
  2. Bermudez MA, Pereira L, Fraile C, et al. Roles of Palmitoleic Acid and Its Positional Isomers, Hypogeic and Sapienic Acids, in Inflammation, Metabolic Diseases and Cancer. Cells 2022;(11).
  3. Stefan N, Kantartzis K, Celebi N, et al. Circulating palmitoleate strongly and independently predicts insulin sensitivity in humans. Diabetes Care 2010;(33):405-407.
  4. Talbot NA, Wheeler-Jones CP, and Cleasby ME. Palmitoleic acid prevents palmitic acid-induced macrophage activation and consequent p38 MAPK-mediated skeletal muscle insulin resistance. Mol Cell Endocrinol 2014;(393):129-142.
  5. Cao H, Gerhold K, Mayers JR, et al. Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism. Cell 2008;(134):933-944.
  6. Cruz MM, Simao JJ, de Sa R, et al. Palmitoleic Acid Decreases Non-alcoholic Hepatic Steatosis and Increases Lipogenesis and Fatty Acid Oxidation in Adipose Tissue From Obese Mice. Front Endocrinol (Lausanne) 2020;(11):537061.
  7. Yang ZH, Miyahara H, and Hatanaka A. Chronic administration of palmitoleic acid reduces insulin resistance and hepatic lipid accumulation in KK-Ay Mice with genetic type 2 diabetes. Lipids Health Dis 2011;(10):120.
  8. de Souza CO, Valenzuela CA, Baker EJ, et al. Palmitoleic Acid has Stronger Anti-Inflammatory Potential in Human Endothelial Cells Compared to Oleic and Palmitic Acids. Mol Nutr Food Res 2018;(62):e1800322.
  9. Yang ZH, Pryor M, Noguchi A, et al. Dietary Palmitoleic Acid Attenuates Atherosclerosis Progression and Hyperlipidemia in Low-Density Lipoprotein Receptor-Deficient Mice. Mol Nutr Food Res 2019;(63):e1900120.
  10. Akazawa Y, Morisaki T, Fukuda H, et al. Significance of serum palmitoleic acid levels in inflammatory bowel disease. Sci Rep 2021;(11):16260.
  11. Chen Y, Mai Q, Chen Z, et al. Dietary palmitoleic acid reprograms gut microbiota and improves biological therapy against colitis. Gut Microbes 2023;(15):2211501.
  12. Menendez JA, and Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer 2007;(7):763-777.
  13. Zhang J, Zhang L, Ye X, et al. Characteristics of fatty acid distribution is associated with colorectal cancer prognosis. Prostaglandins Leukot Essent Fatty Acids 2013;(88):355-360.
  14. Yamasaki M, Chujo H, Nou S, et al. Alleviation of the cytotoxic activity induced by trans10, cis12-conjugated linoleic acid in rat hepatoma dRLh-84 cells by oleic or palmitoleic acid. Cancer Lett 2003;(196):187-196.