Acute regulation of 5′-AMP-activated protein kinase by long-chain fatty acid, glucose and insulin in rat primary adipocytes

Hebbachi, Abdel; Saggerson, David

doi:10.1042/bsr20120031

Cited by 14 publications

(12 citation statements)

References 49 publications

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“…Palmitate stimulated Akt phosphorylation in a time- and dose-dependent manner, and by inhibiting PI3K – which is upstream of Akt in the signal transduction pathway – glucose uptake was abolished by a blocking of Akt phosphorylation. Summarized, these results demonstrate the important role of this signaling pathway in the cell line examined, and similar results have been demonstrated in adipocytes [23]. It is tempting to suggest a similar effect of palmitate on the PI3K/Akt pathway in prostate cancer cells to explain the observations made in our study.…”

Section: Discussionsupporting

confidence: 92%

Influence of free fatty acids on glucose uptake in prostate cancer cells

Andersen

Divilov

Sevak

et al. 2014

Nuclear Medicine and Biology

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Introduction The study focuses on the interaction between glucose and free fatty acids (FFA) in malignant human prostate cancer cell lines by an in vitro observation of uptake of fluoro-2-deoxy-d-glucose (FDG) and acetate. Methods Human prostate cancer cell lines (PC3, CWR22Rv1, LNCaP, and DU145) were incubated for 2 h and 24 h in glucose-containing (5.5 mM) Dulbecco’s Modified Eagle’s Medium (DMEM) with varying concentrations of the free fatty acid palmitate (0–1.0 mM). Then the cells were incubated with [18 F]-FDG (1 µCi/mL; 0.037 MBq/mL) in DMEM either in presence or absence of glucose and in presence of varying concentrations of palmitate for 1 h. Standardized procedures regarding cell counting and measuring for 18F radioactivity were applied. Cell uptake studies with 14C-1-acetate under the same conditions were performed on PC3 cells. Results In glucose containing media there was significantly increased FDG uptake after 24 h incubation in all cell lines, except DU145, when upper physiological levels of palmitate were added. A 4-fold increase of FDG uptake in PC3 cells (15.11% vs. 3.94%/106 cells) was observed in media with 1.0 mM palmitate compared to media with no palmitate. The same tendency was observed in PC3 and CWR22Rv1 cells after 2 h incubation. In glucose-free media no significant differences in FDG uptake after 24 h incubation were observed. The significant differences after 2 h incubation all pointed in the direction of increased FDG uptake when palmitate was added. Acetate uptake in PC3 cells was significantly lower when palmitate was added in glucose-free DMEM. No clear tendency when comparing FDG or acetate uptake in the same media at different time points of incubation was observed. Conclusions Our results indicate a FFA dependent metabolic boost/switch of glucose uptake in PCa, with patterns reflecting the true heterogeneity of the disease.

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Section: Discussionsupporting

confidence: 92%

Influence of free fatty acids on glucose uptake in prostate cancer cells

Andersen

Divilov

Sevak

et al. 2014

Nuclear Medicine and Biology

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“…7). Similar to the effects of glucose and palmitate on AMPK activity in rat adipocytes (35), cardiomyocytes (36), and bovine aortic endothelial cells (91), we found that these nutrients decreased AMPK activity in HAECs. However, activation of AMPK was not sufficient to restore autophagy in this nutrientrich environment.…”

Section: Discussionsupporting

confidence: 55%

“…We and others have shown that high concentrations of glucose or palmitate impair AMPK activity (35,36,91) as well as SIRT1 activity (2,18,71,80). AMPK and SIRT1 have also been shown to regulate one another (11,39,55).…”

Section: Discussionmentioning

confidence: 99%

Glucose and palmitate uncouple AMPK from autophagy in human aortic endothelial cells

Weikel

Cacicedo

Ruderman

et al. 2015

American Journal of Physiology-Cell Physiology

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Weikel KA, Cacicedo JM, Ruderman NB, Ido Y. Glucose and palmitate uncouple AMPK from autophagy in human aortic endothelial cells. Am J Physiol Cell Physiol 308: C249 -C263, 2015. First published October 29, 2014 doi:10.1152/ajpcell.00265.2014.-Dysregulated autophagy and decreased AMP-activated protein kinase (AMPK) activity are each associated with atherogenesis. Atherogenesis is preceded by high circulating concentrations of glucose and fatty acids, yet the mechanism by which these nutrients regulate autophagy in human aortic endothelial cells (HAECs) is not known. Furthermore, whereas AMPK is recognized as an activator of autophagy in cells with few nutrients, its effects on autophagy in nutrient-rich HAECs has not been investigated. We maintained and passaged primary HAECs in media containing 25 mM glucose and incubated them subsequently with 0.4 mM palmitate. These conditions impaired basal autophagy and rendered HAECs more susceptible to apoptosis and adhesion of monocytes, outcomes attenuated by the autophagy activator rapamycin. Glucose and palmitate diminished AMPK activity and phosphorylation of the uncoordinated-51-like kinase 1 (ULK1) at Ser555, an autophagy-activating site targeted by AMPK. 5-Aminoimidazole-4-carboxamide-1-␤-D-ribofuranoside (AICAR)-mediated activation of AMPK phosphorylated acetyl-CoA carboxylase, but treatment with AICAR or other AMPK activators (A769662, phenformin) did not restore ULK1 phosphorylation or autophagosome formation. To determine whether palmitate-induced ceramide accumulation contributed to this finding, we overexpressed a ceramidemetabolizing enzyme, acid ceramidase. The increase in acid ceramidase expression ameliorated the effects of excess nutrients on ULK1 phosphorylation, without altering the effects of the AMPK activators. Thus, unlike low nutrient conditions, AMPK becomes uncoupled from autophagy in HAECs in a nutrient-rich environment, such as that found in patients with increased cardiovascular risk. These findings suggest that combinations of AMPK-independent and AMPK-dependent therapies may be more effective alternatives than either therapy alone for treating nutrient-induced cellular dysfunction. endothelium; autophagy; palmitate; glucose; AMPK PATIENTS WITH THE METABOLIC SYNDROME or type 2 diabetes are more likely to develop cardiovascular complications such as atherosclerosis (26,44,54,62,77). Many cellular processes have been implicated in driving this pathology, but the predominant mechanisms remain unclear. Intriguing reports from humans and murine models of vascular disease indicate that dysregulation of macroautophagy, a pathway by which cellular components are recycled for energy utilization, may play a prominent role in this disease progression. Thus it has been shown that impairment of macroautophagy contributes to arterial aging (56), cardiomyocyte apoptosis (34), and aortic lesion formation (74).Macroautophagy (hereinafter referred to as "autophagy") is a process by which cellular components are engulfed in a double-membraned vesicle, the au...

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“…The PI3K inhibitor (wortmannin) hardly affected induction of CYP3A4 by PA. Several studies demonstrated that PA and OA induced both NFkB (57,58) and PKC activities (59,60), and the stimulatory effects of OA on the PKC pathway was stronger than those of PA (61,62). PA was also reported to inhibit phosphorylation of AMPK (63,64) and Akt (65,66). In sharp contrast, OA enhanced the activity of Akt (67) and showed weak inhibition on phosphorylation of AMPK (68).…”

Section: Discussionmentioning

confidence: 99%

Increased Levels of Fatty Acids Contributed to Induction of Hepatic CYP3A4 Activity Induced by Diabetes — In Vitro Evidence From HepG2 Cell and Fa2N-4 Cell Lines

Duan

et al. 2014

J Pharmacol Sci

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Abstract.Accumulating evidences have shown that diabetes upregulated the function and expression of CYP3A4, but the mechanism remained unclear. In this study, HepG2 cells were incubated with serum from diabetic rats induced by streptozotocin, and the activity of CYP3A4 was measured by substrate metabolism. Results showed that incubation with diabetic serum significantly induced CYP3A4 activity in HepG2 cells. To identify the specific factors contribut ing to the regulation, the abnormally altered components in diabetic serum, including glucose, insulin, cholesterol, and free fatty acids were screened. It was found that only fatty acids concen trationdependently upregulated CYP3A4 activity, and the induction by fatty acids was further confirmed in Fa2N4 cells. Data from western blotting and QTPCR showed that induction of CYP3A4 activity was associated with upregulation of CYP3A4 protein and mRNA levels. In addition, effects of pharmacological inhibitors on fatty acid-induced CYP3A4 activity were studied. The results indicated that the induction of CYP3A4 activity by oleic acid may be partly via AMPK, PKC, and NFkB-dependent pathways, whereas that by palmitic acid was possibly associated with the PKCdependent pathway. In conclusion, the increased levels of fatty acids may be one of the reasons leading to the elevated function and expression of CYP3A4 under diabetic conditions.

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Acute regulation of 5′-AMP-activated protein kinase by long-chain fatty acid, glucose and insulin in rat primary adipocytes

Cited by 14 publications

References 49 publications

Influence of free fatty acids on glucose uptake in prostate cancer cells

Influence of free fatty acids on glucose uptake in prostate cancer cells

Glucose and palmitate uncouple AMPK from autophagy in human aortic endothelial cells

Increased Levels of Fatty Acids Contributed to Induction of Hepatic CYP3A4 Activity Induced by Diabetes — In Vitro Evidence From HepG2 Cell and Fa2N-4 Cell Lines

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