Induction of miR‐29a by saturated fatty acids impairs insulin signaling and glucose uptake through translational repression of IRS‐1 in myocytes

Yang, Won-Mo; Jeong, Hyo‐Jin; Park, Seung-Yoon; Lee, Wan

doi:10.1016/j.febslet.2014.05.011

Cited by 93 publications

(81 citation statements)

References 42 publications

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“…The knockdown of NLRP3 by RNA interference significantly inhibited insulin resistance which is typically induced in PLIN2-overexpressing C2C12 cells, suggesting that the NLRP3 inflammasome mediates PLIN2-induced insulin resistance. Decreased levels of IRS-1 have been reported to alter insulin signaling in adipocytes and myocytes (24,25). In this study, we observed that IRS-1 expression was decreased in C2C12 cells that overexpressed PLIN2 in the context of insulin exposure, whereas NLRP3 knockdown increased the expression of IRS-1.…”

Section: Discussionmentioning

confidence: 49%

“…IRS-1, one of the major substrates of the insulin receptor kinase, is essential for the activatation of PI3K in response to insulin, which leads to the phosphorylation of protein kinase B (also known as Akt) and subsequent glucose uptake (23). The downregulation of IRS-1 seems to be the major mechanism involved in the alteration of insulin signaling and glucose transport (24). Thus, we examined the effects of PLIN2 and NLRP3 manipulations on the mRNA expression levels of IRS-1 in the C2C12 cells.…”

Section: Suppression Of Irs-1 By Il-1β Mediates the Effects Of The Nlrp3mentioning

confidence: 99%

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PLIN2 inhibits insulin-induced glucose uptake in myoblasts through the activation of the NLRP3 inflammasome

Cho

Kang

2015

International Journal of Molecular Medicine

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Abstract. Impaired lipid metabolism and inflammatory pathways have individually been implicated in the development of insulin resistance in skeletal muscle; however, little evidence is available to date linking the two in this context. In this study, we explored a potential molecular mechanism underlying insulin resistance in myoblasts mediated by the crosstalk between lipid accumulation and inflammatory pathways. We examined the influence of perilipin 2 (PLIN2), one of the most highly expressed lipid droplet-associated proteins in skeletal muscle, on glucose uptake and on the nucleotide-binding domain, leucine-rich repeat containing protein 3 (NLRP3) inflammasome in vitro. PLIN2 overexpression in C2C12 cells led to an increased expression of NLRP3, caspase-1 and interleukin (IL)-1β, along with an impaired insulin-induced glucose uptake. This defect was remedied by the RNAi-mediated knockdown of NLRP3 expression. We also found that insulin receptor substrate-1 (IRS-1), a component of insulin signaling, was negatively regulated by NLRP3 and IL-1β, and that IL-1β inhibited insulin-induced glucose uptake in myoblasts. These results suggest that PLIN2 inhibits insulin-induced glucose uptake by activating NLRP3, caspase-1 and IL-1β, leading to a decreased IRS-1 expression. This study provides in vitro evidence supporting an association between lipid metabolism and inflammatory pathways in the pathogenesis of insulin resistance in skeletal muscle, and suggests potential therapeutic targets that warrant further investigation.

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Section: Discussionmentioning

confidence: 49%

Section: Suppression Of Irs-1 By Il-1β Mediates the Effects Of The Nlrp3mentioning

confidence: 99%

PLIN2 inhibits insulin-induced glucose uptake in myoblasts through the activation of the NLRP3 inflammasome

Cho

Kang

2015

International Journal of Molecular Medicine

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“…115,116 Although this remains highly controversial, [117][118][119] host-derived small RNAs are known to regulate many processes of relevance to cardiometabolic risk 120 and to be altered in response to dietary intervention and specific nutrients. 121,122 For example, several microRNAs were reported to be changed in the PBMC transcriptome after 1 year of supplementation with resveratrolcontaining grapeseed extract in subjects with type 2 diabetes mellitus. 123 Thus, the potential functional role of diet acting directly or indirectly through small RNA is intriguing.…”

Section: Noncoding Rnamentioning

confidence: 99%

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

Ferguson¹,

Allayee²,

Gerszten³

et al. 2016

Circ Cardiovasc Genet

101

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Abstract-Cardiometabolic diseases are the leading cause of death worldwide and are strongly linked to both genetic and nutritional factors. The field of nutrigenomics encompasses multiple approaches aimed at understanding the effects of diet on health or disease development, including nutrigenetic studies investigating the relationship between genetic variants and diet in modulating cardiometabolic risk, as well as the effects of dietary components on multiple "omic" measures, including transcriptomics, metabolomics, proteomics, lipidomics, epigenetic modifications, and the microbiome. Here, we describe the current state of the field of nutrigenomics with respect to cardiometabolic disease research and outline a direction for the integration of multiple omics techniques in future nutrigenomic studies aimed at understanding mechanisms and developing new therapeutic options for cardiometabolic disease treatment and prevention. The interpretation and scope of nutrigenomics may vary, but it can be thought to encompass the spectrum of nutritional genomics research, including classic nutrigenetics studies of gene-diet interactions and molecular nutrition, in vitro and in vivo models, human nutrition studies, and the application of largescale, unbiased studies using high-throughput "omics" techniques to study the effects of nutrients on the body. 6 As the Figure shows, diet and the genome may influence cardiometabolic health through a variety of interconnected intermediates, perturbations in which can be measured through omics technologies, including RNA expression (transcriptome), epigenetic modifications (epigenome), metabolites (metabolome), lipids (lipidome), proteins (proteome), and resident microbial communities (microbiome). Although it is clear that both nutrients and genes play a distinct role in determining health, the complex interactions among genes, diet, and downstream networks are not well understood. The application of nutrigenomics approaches to questions of human health and disease is an important component in understanding the complexities of the interplay between basic metabolic processes and externalThe American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on January 22, 2016, and the American Heart Association Executive Committee on February 23, 2016. A copy of the document is available at http://professional.heart.org/statements by using either "Search for Guidelines & Statements" or the "Browse by Topic" area. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@ wolterskluwer.com.The...

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“…However, it is unclear if and how miR-29a is linked to the regulation of insulin sensitivity in the skeletal muscle. We have found that the expression of miR-29a was up-regulated in the skeletal muscle, liver and serum of HFD-fed mice (60% kcal from fat for 14 weeks) [12] . In addition, the cellular treatment of SFA palmitate in myocytes increased the level of miR-29a expression [12] .…”

Section: Introductionmentioning

confidence: 89%

“…Moreover, the plasma or tissue levels of those miRNAs might be associated with the insulin sensitivity of humans, thereby allowing the development of miRNAs as potential new diagnostic and therapeutic targets in insulin resistance and T2DM [3,5] . Previous our studies unveiled that the certain miRNAs, such as miR-29a and miR-195, were increased in the skeletal muscle and liver of high fat diet (HFD)-fed mice with insulin resistance [12,13] . Hence, we investigated whether these miRNAs could be induced by SFA, and whether these miRNAs might actively participate in SFA-induced insulin resistance.…”

Section: Introductionmentioning

confidence: 94%

Implication of Saturated Fatty Acids-induced MicroRNAs in Insulin Resistance and Diabetes

Yang¹,

Lee

2015

RNA Dis

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Induction of miR‐29a by saturated fatty acids impairs insulin signaling and glucose uptake through translational repression of IRS‐1 in myocytes

Cited by 93 publications

References 42 publications

PLIN2 inhibits insulin-induced glucose uptake in myoblasts through the activation of the NLRP3 inflammasome

PLIN2 inhibits insulin-induced glucose uptake in myoblasts through the activation of the NLRP3 inflammasome

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

Implication of Saturated Fatty Acids-induced MicroRNAs in Insulin Resistance and Diabetes

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