Pentadecanoic acid promotes basal and insulin-stimulated glucose uptake in C2C12 myotubes

  • Wen-Cheng Fu School of Life Sciences, East China Normal University, Shanghai, China
  • Hai-Yan Li School of Life Sciences, East China Normal University, Shanghai, China
  • Tian-Tian Li School of Life Sciences, East China Normal University, Shanghai, China
  • Kuo Yang School of Life Sciences, East China Normal University, Shanghai, China
  • Jia-Xiang Chen School of Life Sciences, East China Normal University, Shanghai, China
  • Si-Jia Wang School of Life Sciences, East China Normal University, Shanghai, China
  • Chun-Hui Liu China National Institute of Standardization, Beijing, China
  • Wen Zhang School of Life Sciences, East China Normal University, Shanghai, China
Keywords: Pentadecanoic acid; glucose uptake; AMP-activated protein kinase; insulin sensitivity; C2C12 myotubes


Background: Saturated fatty acids (SFAs) generally have been thought to worsen insulin-resistance and increase the risk of developing type 2 diabetes mellitus (T2DM). Recently, accumulating evidence has revealed that SFAs are not a single homogeneous group, instead different SFAs are associated with T2DM in opposing directions. Pentadecanoic acid (C15:0, PA) is directly correlated with dairy products, and a negative association between circulating PA and metabolic disease risk was observed in epidemiological studies. Therefore, the role of PA in human health needs to be reinforced. Whether PA has a direct benefit on glucose metabolism and insulin sensitivity needs further investigation.

Objective: The present study aimed to investigate the effect and potential mechanism of action of PA on basal and insulin stimulated glucose uptake in C2C12 myotubes.

Methods: Glucose uptake was determined using a 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake assay. Cell membrane proteins were isolated and glucose transporter 4 (GLUT4) protein was detected by western blotting to examine the translocation of GLUT4 to the plasma membrane. The phosphorylation levels of proteins involved in the insulin and 5'-adenosine monophosphate-activated protein kinase (AMPK) pathways were examined by western blotting.

Results: We found that PA significantly promoted glucose uptake and GLUT4 translocation to the plasma membrane. Mechanistically, PA had no effect on the insulin-dependent pathway involving insulin receptor substrate (Tyr632) and Akt, but increased phosphorylation of AMPK and Akt substrate of 160 kDa (AS160). Compound C (an AMPK inhibitor) blocked PA-induced AMPK activation and reversed PA-induced GLUT4 translocation, indicating that PA promotes glucose uptake via the AMPK pathway in vitro. Moreover, PA significantly promoted insulin-stimulated glucose uptake in myotubes. Under insulin stimulation, PA did not affect the insulin-dependent pathway, but still activated AMPK.

Conclusion: PA, an odd-chain saturated fatty acid, significantly stimulates glucose uptake via the AMPK-AS160 pathway and exhibits an insulin-sensitizing effect in myotubes.


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How to Cite
Fu, W.-C., Li, H.-Y., Li, T.-T., Yang, K., Chen, J.-X., Wang, S.-J., Liu, C.-H., & Zhang, W. (2021). Pentadecanoic acid promotes basal and insulin-stimulated glucose uptake in C2C12 myotubes. Food & Nutrition Research, 65.
Original Articles