Trans-palmitoleic acid, a dairy fat biomarker, stimulates insulin secretion and activates G protein-coupled receptors with a different mechanism from the cis isomer

Abstract

Dietary trans palmitoleic acid (trans 16:1n–7, tPOA), a biomarker for high-fat dairy product intake, has been associated with a lower risk of type 2 diabetes mellitus (T2DM) in some cross-sectional...

Lysophosphatidylcholines Enriched with cis and trans Palmitoleic Acid Regulate Insulin Secretion via GPR119 Receptor

“…Our recent findings confirm the insulin secretagogue properties of the C16:1­(9 Z ) isomer and show that this biological function depends on the activation of GPR40, GPR55, GPR119, and GPR120 receptors . All these GPCRs are considered potential targets for the pharmacological management of diabetes. − The C16:1­(9 E ) isomer also augments insulin release from pancreatic β cells but signals not only through G q as observed with the endogenous lipid ligands, including C16:1­(9 Z ), but also through G s …”

“…34 Also, our previous findings show that both isomers C16:1(E9) and C16:1(Z9) enhance glucose-stimulated insulin secretion, but they achieve it with different intracellular signaling pathways. 16 In conclusion, the results presented here are the very first that comprehensively show the biological effect, manifested as enhanced insulin secretion during glucose stimulation, of two different isomers of palmitoleic acid incorporated into LPC. We were able to indicate that LPC(16:1(9Z)) and LPC(16:1-(9E)), despite the differences in cytotoxicity and CMC value, act as GPR55 and GPR119 ligands and they activate G s cascade presented as cAMP accumulation.…”

“…In contrast, C18:2­( Z 9 E 11) inhibits tumor necrosis factor-α production and suppresses the generation of neurotoxic amyloid β but C18:2­( E 10 Z 12) does not. , Moreover, diet supplementation with C18:2­( Z 9 E 11) results in the growth of LPC­(C18:2­( Z 9 E 11)) content in neurons . Also, our previous findings show that both isomers C16:1­( E 9) and C16:1­( Z 9) enhance glucose-stimulated insulin secretion, but they achieve it with different intracellular signaling pathways …”

“…12−15 The C16:1(9E) isomer also augments insulin release from pancreatic β cells but signals not only through G q as observed with the endogenous lipid ligands, including C16:1(9Z), but also through G s . 16 If the difference in acyl group conformation in POA affects receptor activation in the context of GPCR signaling, then we decided to investigate whether the double bond configuration of the acyl tail also influences the mode of LPC binding with GPR40, GPR55, GPR119, and GPR120. Although Xu et al identified LPC(16:1) (isomer not specified) inside the GPR119 ligand pocket, they did not investigate its role in receptor activation thoroughly.…”

“…Subsequently, the human pancreatic β cell line, EndoC-βH1, was used as a model to confirm molecular modeling showing preferential binding to GPR119 and to determine the impact of LPC­(16:1­(9 Z )) and LPC­(16:1­(9 E )) on glucose-stimulated insulin secretion. We have previously demonstrated the expression of GPR40 , GPR55 , GPR119 , and GPR120 in EndoC-βH1 cells . Since trans fatty acids resemble the linear form of saturated fat, we also included LPC(16:0) in biological investigations.…”