Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Lipids Health Dis
2014 Dec 20;13:199. doi: 10.1186/1476-511X-13-199.
Show Gene links
Show Anatomy links
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.
Amengual,
Induction of carnitine palmitoyl transferase 1 and fatty acid oxidation by retinoic acid in HepG2 cells.
2013, Pubmed
Amengual,
Induction of carnitine palmitoyl transferase 1 and fatty acid oxidation by retinoic acid in HepG2 cells.
2013,
Pubmed
Bazin,
Assays of lipogenic enzymes.
2001,
Pubmed
Bijland,
Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation.
2013,
Pubmed
Bolsoni-Lopes,
Palmitoleic acid (n-7) increases white adipocyte lipolysis and lipase content in a PPARα-dependent manner.
2013,
Pubmed
Brooks,
Effects of hormones on the rate of the triacylglycerol/fatty acid substrate cycle in adipocytes and epididymal fat pads.
1983,
Pubmed
Bryant,
Regulated transport of the glucose transporter GLUT4.
2002,
Pubmed
Cao,
Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism.
2008,
Pubmed
Ceddia,
The role of AMP-activated protein kinase in regulating white adipose tissue metabolism.
2013,
Pubmed
DiGirolamo,
Lactate production in adipose tissue: a regulated function with extra-adipose implications.
1992,
Pubmed
Diakogiannaki,
Mechanisms involved in the cytotoxic and cytoprotective actions of saturated versus monounsaturated long-chain fatty acids in pancreatic beta-cells.
2007,
Pubmed
Dimopoulos,
Differential effects of palmitate and palmitoleate on insulin action and glucose utilization in rat L6 skeletal muscle cells.
2006,
Pubmed
Duncan,
Regulation of lipolysis in adipocytes.
2007,
Pubmed
Festuccia,
Depot-specific effects of the PPARgamma agonist rosiglitazone on adipose tissue glucose uptake and metabolism.
2009,
Pubmed
Gaidhu,
Prolonged AICAR-induced AMP-kinase activation promotes energy dissipation in white adipocytes: novel mechanisms integrating HSL and ATGL.
2009,
Pubmed
Gauthier,
AMP-activated protein kinase is activated as a consequence of lipolysis in the adipocyte: potential mechanism and physiological relevance.
2008,
Pubmed
Govers,
Molecular mechanisms of GLUT4 regulation in adipocytes.
2015,
Pubmed
Hernandez,
Akt mediates insulin induction of glucose uptake and up-regulation of GLUT4 gene expression in brown adipocytes.
2001,
Pubmed
Hirabara,
Saturated fatty acid-induced insulin resistance is associated with mitochondrial dysfunction in skeletal muscle cells.
2009,
Pubmed
Huang,
Pachymic acid stimulates glucose uptake through enhanced GLUT4 expression and translocation.
2011,
Pubmed
Jaworski,
Regulation of triglyceride metabolism. IV. Hormonal regulation of lipolysis in adipose tissue.
2007,
Pubmed
Jäger,
AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha.
2007,
Pubmed
Kramer,
Distinct signals regulate AS160 phosphorylation in response to insulin, AICAR, and contraction in mouse skeletal muscle.
2006,
Pubmed
Liu,
The AMPK inhibitor compound C is a potent AMPK-independent antiglioma agent.
2014,
Pubmed
McGee,
AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5.
2008,
Pubmed
Mercader,
All-trans retinoic acid increases oxidative metabolism in mature adipocytes.
2007,
Pubmed
Morgan,
Unsaturated fatty acids as cytoprotective agents in the pancreatic beta-cell.
2010,
Pubmed
Newsholme,
Reflections on the mechanism of action of hormones.
1980,
Pubmed
Obanda,
Modulation of cellular insulin signaling and PTP1B effects by lipid metabolites in skeletal muscle cells.
2014,
Pubmed
Papa,
Loss of weight restores GLUT 4 content in insulin-sensitive tissues of monosodium glutamate-treated obese mice.
1998,
Pubmed
Parillo,
Diet composition and the risk of type 2 diabetes: epidemiological and clinical evidence.
2004,
Pubmed
Park,
Phosphorylation of C/EBPbeta at a consensus extracellular signal-regulated kinase/glycogen synthase kinase 3 site is required for the induction of adiponectin gene expression during the differentiation of mouse fibroblasts into adipocytes.
2004,
Pubmed
RODBELL,
METABOLISM OF ISOLATED FAT CELLS. I. EFFECTS OF HORMONES ON GLUCOSE METABOLISM AND LIPOLYSIS.
1996,
Pubmed
Reynoso,
High levels of palmitic acid lead to insulin resistance due to changes in the level of phosphorylation of the insulin receptor and insulin receptor substrate-1.
2004,
Pubmed
Richter,
Exercise, GLUT4, and skeletal muscle glucose uptake.
2013,
Pubmed
Sano,
Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation.
2003,
Pubmed
Shepherd,
Glucose transporters and insulin action--implications for insulin resistance and diabetes mellitus.
1999,
Pubmed
Smith,
AMP kinase activation with AICAR simultaneously increases fatty acid and glucose oxidation in resting rat soleus muscle.
2005,
Pubmed
Sullivan,
Inhibition of lipolysis and lipogenesis in isolated rat adipocytes with AICAR, a cell-permeable activator of AMP-activated protein kinase.
1994,
Pubmed
Wolfe,
Role of triglyceride-fatty acid cycle in controlling fat metabolism in humans during and after exercise.
1990,
Pubmed
Wood,
Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins.
2003,
Pubmed
Wu,
Involvement of AMP-activated protein kinase in glucose uptake stimulated by the globular domain of adiponectin in primary rat adipocytes.
2003,
Pubmed
Yang,
Chronic administration of palmitoleic acid reduces insulin resistance and hepatic lipid accumulation in KK-Ay Mice with genetic type 2 diabetes.
2011,
Pubmed
de Castro Barbosa,
Potential role of growth hormone in impairment of insulin signaling in skeletal muscle, adipose tissue, and liver of rats chronically treated with arginine.
2009,
Pubmed
