Oleate dose-dependently regulates palmitate metabolism and insulin signaling in C2C12 myotubes

Capel, Frédéric; Cheraiti, Naoufel; Acquaviva, Cécile; Hénique, Carole; Bertrand‐Michel, Justine; Vianey‐Saban, Christine; Prip‐Buus, Carina; Morio, Béatrice

doi:10.1016/j.bbalip.2016.10.002

Cited by 28 publications

(35 citation statements)

References 48 publications

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“…Augmented basal Akt phosphorylation has been linked to the development of insulin resistance, as increased basal p-Akt expression aggravates ubiquitous fat accumulation, suppresses mitochondrial production, and enhances oxidative stress and insulin resistance (29). The protective effects of oleate observed here are in line with the existing literature (26,(30)(31)(32)(33). Given the attenuation of Akt phosphorylation induced primarily by palmitate, we proceeded to examine insulinstimulated glucose uptake in control, FIT2 knockdown as well as negative control (Scr) adipocytes, with and without palmitate treatment (Fig.…”

Section: Tag Accumulation Capacity Is Reduced In Fit2 Protein Knockdosupporting

confidence: 87%

Fat storage‐inducing transmembrane protein 2 (FIT2) is less abundant in type 2 diabetes, and regulates triglyceride accumulation and insulin sensitivity in adipocytes

et al. 2018

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Fat storage-inducing transmembrane protein 2 (FIT2) aids in partitioning of cellular triacylglycerol into lipid droplets. A genome-wide association study reported FITM2-R3H domain containing like-HNF4A locus to be associated with type 2 diabetes (T2DM) in East Asian populations. Mice with adipose tissue (AT)-specific FIT2 knockout exhibited lipodystrophic features, with reduced AT mass, insulin resistance, and greater inflammation in AT when fed a high-fat diet. The role of FIT2 in regulating human adipocyte function is not known. Here, we found FIT2 protein abundance is lower in subcutaneous and omental AT obtained from patients with T2DM compared with nondiabetic control subjects. Partial loss of FIT2 protein in primary human adipocytes attenuated their lipid storage capacity and induced insulin resistance. After palmitate treatment, triacylglycerol accumulation, insulin-induced Akt (Ser-473) phosphorylation, and insulin-stimulated glucose uptake were significantly reduced in FIT2 knockdown adipocytes compared with control cells. Gene expression of proinflammatory cytokines IL-18 and IL-6 and phosphorylation of the endoplasmic reticulum stress marker inositol-requiring enzyme 1α were greater in FIT2 knockdown adipocytes than in control cells. Our results show for the first time that FIT2 is associated with T2DM in humans and plays an integral role in maintaining metabolically healthy AT function.-Agrawal, M., Yeo, C. R., Shabbir, A., Chhay, V., Silver, D. L., Magkos, F., Vidal-Puig, A., Toh, S.-A. Fat storage-inducing transmembrane protein 2 (FIT2) is less abundant in type 2 diabetes, and regulates triglyceride accumulation and insulin sensitivity in adipocytes.

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Section: Tag Accumulation Capacity Is Reduced In Fit2 Protein Knockdosupporting

confidence: 87%

Fat storage‐inducing transmembrane protein 2 (FIT2) is less abundant in type 2 diabetes, and regulates triglyceride accumulation and insulin sensitivity in adipocytes

et al. 2018

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“…Our results shed new light on the contribution of FA oxidation in MCF‐7 cells where pharmacological inhibition of FA oxidation sensitized MCF‐7 cells to palmitate‐induced apoptosis and suggests that targeting FA oxidation is an attractive therapeutic strategy in BrCa. The addition or presence of oleate ameliorates the cytotoxic effects of palmitate (Capel et al ., 2016; Colvin et al ., 2017; Kim et al ., 2017; Kwon and Querfurth, 2015; Penke et al ., 2017; Sargsyan et al ., 2016). Proposed mechanisms for these observations include attenuating palmitate‐induced ER stress (Colvin et al ., 2017), preventing activation of the unfolded protein response (Sommerweiss et al ., 2013), activating prosurvival pathways of ER stress (Sargsyan et al ., 2016), restoring insulin stimulated protein kinase B (Akt) signaling (Capel et al ., 2016), and activating AMP‐activated protein kinase and mechanistic target of rapamycin signaling (Kwon and Querfurth, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Proposed mechanisms for these observations include attenuating palmitate‐induced ER stress (Colvin et al ., 2017), preventing activation of the unfolded protein response (Sommerweiss et al ., 2013), activating prosurvival pathways of ER stress (Sargsyan et al ., 2016), restoring insulin stimulated protein kinase B (Akt) signaling (Capel et al ., 2016), and activating AMP‐activated protein kinase and mechanistic target of rapamycin signaling (Kwon and Querfurth, 2015). Oleate treatment in a range of cells also modulates palmitate metabolism including stimulating TAG synthesis, preventing diacylglycerol accumulation (Capel et al ., 2016; Kwon et al ., 2014), and preventing mitochondrial reactive oxygen species production and dysfunction (Kwon et al ., 2014). These observations were predominantly made by cotreatment with oleate and palmitate.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity of fatty acid metabolism in breast cancer cells underlies differential sensitivity to palmitate‐induced apoptosis

et al. 2018

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Breast cancer (BrCa) metabolism is geared toward biomass synthesis and maintenance of reductive capacity. Changes in glucose and glutamine metabolism in BrCa have been widely reported, yet the contribution of fatty acids (FAs) in BrCa biology remains to be determined. We recently reported that adipocyte coculture alters MCF‐7 and MDA‐MB‐231 cell metabolism and promotes proliferation and migration. Since adipocytes are FA‐rich, and these FAs are transferred to BrCa cells, we sought to elucidate the FA metabolism of BrCa cells and their response to FA‐rich environments. MCF‐7 and MDA‐MB‐231 cells incubated in serum‐containing media supplemented with FAs accumulate extracellular FAs as intracellular triacylglycerols (TAG) in a dose‐dependent manner, with MDA‐MB‐231 cells accumulating more TAG. The differences in TAG levels were a consequence of distinct differences in intracellular partitioning of FAs, and not due to differences in the rate of FA uptake. Specifically, MCF‐7 cells preferentially partition FAs into mitochondrial oxidation, whereas MDA‐MB‐231 cells partition FAs into TAG synthesis. These differences in intracellular FA handling underpin differences in the sensitivity to palmitate‐induced lipotoxicity, with MDA‐MB‐231 cells being highly sensitive, whereas MCF‐7 cells are partially protected. The attenuation of palmitate‐induced lipotoxicity in MCF‐7 cells was reversed by inhibition of FA oxidation. Pretreatment of MDA‐MB‐231 cells with FAs increased TAG synthesis and reduced palmitate‐induced apoptosis. Our results provide novel insight into the potential influences of obesity on BrCa biology, highlighting distinct differences in FA metabolism in MCF‐7 and MDA‐MB‐231 cells and how lipid‐rich environments modulate these effects.

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“…Enhanced channelling of FA substrate to TAG can reduce lipotoxic pressure despite greater cellular lipid content (Listenberger et al 2003, Coll et al 2008, Henique et al 2010, Capel et al 2016. Indeed, the apparently futile, ATP-consuming cycle of FA re-esterification to TAGs during adipocyte lipolysis appears designed to protect cells from lipotoxic stress (Chitraju et al 2017); in β-cells, this cycle may regulate insulin secretion (Corkey et al 2000, Nolan et al 2006, Fex & Mulder 2008.…”

Section: Mediators Of Lipid-induced Ir -Many Culprits For the Same Crmentioning

confidence: 99%

Defining lipid mediators of insulin resistance: controversies and challenges

Metcalfe

Smith

Turner

2019

Journal of Molecular Endocrinology

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Essential elements of all cells, lipids play important roles in energy production, signalling and as structural components. Despite these critical functions, excessive availability and intracellular accumulation of lipid is now recognised as a major factor contributing to many human diseases, including obesity and diabetes. In the context of these metabolic disorders, ectopic deposition of lipid has been proposed to have deleterious effects of insulin action. While this relationship has been recognised for some time now, there is currently no unifying mechanism to explain how lipids precipitate the development of insulin resistance. This review summarises the evidence linking specific lipid molecules to the induction of insulin resistance, describing some of the current controversies and challenges for future studies in this field.

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Oleate dose-dependently regulates palmitate metabolism and insulin signaling in C2C12 myotubes

Cited by 28 publications

References 48 publications

Fat storage‐inducing transmembrane protein 2 (FIT2) is less abundant in type 2 diabetes, and regulates triglyceride accumulation and insulin sensitivity in adipocytes

Fat storage‐inducing transmembrane protein 2 (FIT2) is less abundant in type 2 diabetes, and regulates triglyceride accumulation and insulin sensitivity in adipocytes

Heterogeneity of fatty acid metabolism in breast cancer cells underlies differential sensitivity to palmitate‐induced apoptosis

Defining lipid mediators of insulin resistance: controversies and challenges

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