Palmitoleic acid (n-7) increases white adipocytes GLUT4 content and glucose uptake in association with AMPK activation.

Andressa Bolsoni-Lopes,Maria Isabel C Alonso-Vale,Paula B Andrade,Maysa M Cruz,Sandro M Hirabara,Patricia Chimin,Francisco L Torres-Leal,Talita Sm Farias,William T Festuccia,Fabio B Lima

doi:10.1186/1476-511x-13-199

Andressa Bolsoni-Lopes, Maria Isabel C Alonso-Vale + Show 8 more

Open Access

https://doi.org/10.1186/1476-511x-13-199

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Abstract

BackgroundPalmitoleic acid was previously shown to improve glucose homeostasis by reducing hepatic glucose production and by enhancing insulin-stimulated glucose uptake in skeletal muscle. Herein we tested the hypothesis that palmitoleic acid positively modulates glucose uptake and metabolism in adipocytes.MethodsFor this, both differentiated 3 T3-L1 cells treated with either palmitoleic acid (16:1n7, 200 μM) or palmitic acid (16:0, 200 μM) for 24 h and primary adipocytes from mice treated with 16:1n7 (300 mg/kg/day) or oleic acid (18:1n9, 300 mg/kg/day) by gavage for 10 days were evaluated for glucose uptake, oxidation, conversion to lactate and incorporation into fatty acids and glycerol components of TAG along with the activity and expression of lipogenic enzymes.ResultsTreatment of adipocytes with palmitoleic, but not oleic (in vivo) or palmitic (in vitro) acids, increased basal and insulin-stimulated glucose uptake and GLUT4 mRNA levels and protein content. Along with uptake, palmitoleic acid enhanced glucose oxidation (aerobic glycolysis), conversion to lactate (anaerobic glycolysis) and incorporation into glycerol-TAG, but reduced de novo fatty acid synthesis from glucose and acetate and the activity of lipogenic enzymes glucose 6-phosphate dehydrogenase and ATP-citrate lyase. Importantly, palmitoleic acid induction of adipocyte glucose uptake and metabolism were associated with AMPK activation as evidenced by the increased protein content of phospho(p)Thr172AMPKα, but no changes in pSer473Akt and pThr308Akt. Importantly, such increase in GLUT4 content induced by 16:1n7, was prevented by pharmacological inhibition of AMPK with compound C.ConclusionsIn conclusion, palmitoleic acid increases glucose uptake and the GLUT4 content in association with AMPK activation.

Highlights

Palmitoleic acid was previously shown to improve glucose homeostasis by reducing hepatic glucose production and by enhancing insulin-stimulated glucose uptake in skeletal muscle
In an attempt to investigate whether palmitoleic acid enhances glucose uptake by acting directly on adipocytes and, if so, to unveil mechanisms underlying this action, we evaluated the effects of this fatty acid on 3 T3-L1 adipocytes glucose uptake in vitro
In an attempt to unveil the mechanisms underlying the above described 16:1n7 actions in adipocytes, we investigated the effects of this fatty acid on the activation status of major intracellular signaling proteins, namely Akt and AMPK, previously implicated in the regulation of glucose uptake and metabolism

Summary

Introduction

Palmitoleic acid was previously shown to improve glucose homeostasis by reducing hepatic glucose production and by enhancing insulin-stimulated glucose uptake in skeletal muscle. GLUT4 to the plasma membrane [6,7] induced by activation of the canonical insulin receptor substrate (IRS) phosphoinositide 3-kinase (PI3K) - Akt pathway [7,8,9]. Insulin through the very same IRS-PI3K-Akt pathway modulates GLUT4 protein content [10,11]. Another intracellular signaling pathway that plays an important role in the regulation of glucose uptake in adipocytes is the AMP-activated protein kinase (AMPK) [12,13], a heterotrimeric protein that is activated by the lower ATP/AMP ratio commonly found in situations of higher energy demand. AMPK positively modulates GLUT4 transcription and protein levels [16]

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Conclusion