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Lipids Health Dis
2014 Dec 20;13:199. doi: 10.1186/1476-511X-13-199.
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Palmitoleic acid (n-7) increases white adipocytes GLUT4 content and glucose uptake in association with AMPK activation.
Bolsoni-Lopes A
,
Festuccia WT
,
Chimin P
,
Farias TS
,
Torres-Leal FL
,
Cruz MM
,
Andrade PB
,
Hirabara SM
,
Lima FB
,
Alonso-Vale MI
.
Abstract
BACKGROUND: Palmitoleic 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.
METHODS: For 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.
RESULTS: Treatment 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.
CONCLUSIONS: In conclusion, palmitoleic acid increases glucose uptake and the GLUT4 content in association with AMPK activation.
Figure 4.
Basal and insulin-stimulated rates of acetate (Panel A) and glucose (Panel B) incorporation in fatty acids of triacylglycerol and maximal activities of ATP citrate lyase (ACL, Panel C), fatty acid synthase (FAS, Panel D) and glucose-6-phosphate dehydrogenase (G6PDH, Panel E), in differentiated 3 T3-L1 cells treated for 24 h with either vehicle, palmitic acid (16:0, 200 μM) or palmitoleic acid (16:1n7, 200 μM). Results are means ± SE (n = 6-8/group). *P < 0.05 vs. vehicle and #P < 0.05 vs. 16:0.
Figure 5.
Basal protein content of phospho(p) Ser473 Akt and pThr308Akt (Panel A) and pThr172 AMP-activatedprotein kinase alpha (Panel B) in differentiated 3 T3-L1 cells treated for 24 h with either vehicle, palmitic acid (16:0, 200 μM) or palmitoleic acid (16:1n7, 200 μM). Basal protein content of glucose transporter 4 (GLUT4, Panel C) in differentiated 3 T3-L1 cells treated for 24 h with either vehicle, palmitoleic acid (16:1n7, 200 μM), Compound C (Comp. C, 20 μM) or palmitoleic acid associated with Compound C (Comp. C + 16:1n7). Results are means ± SE (n = 3-4/group). *P < 0.05 16:1n7 vs. all groups.
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