Silencing Jnk1 and Jnk2 accelerates basal lipolysis and promotes fatty acid re-esterification in mouse adipocytes

Rozo, Andrea V.; Vijayvargia, Ravi; Weiss, Harvey R.; Ruan, Hong

doi:10.1007/s00125-008-1036-6

Cited by 23 publications

(18 citation statements)

References 43 publications

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“…Regarding the role of JNK activation in the regulation of lipolysis, it was described that JNK1/JNK2 defi ciency drastically enhanced basal lipolysis ( 24 ). In this context, our data show that incubation with the JNK inhibitor SP600125 (2 h) stimulates the phosphorylation of HSL at Ser 563 and Ser 660 as well as phospho-PKA substrate/perilipin ratio, supporting the idea that JNK inhibition leads to increased lipolysis.…”

supporting

confidence: 84%

“…In addition to the PKAmediated phosphorylation, HSL may be phosphorylated by other kinases, such as extracellular signal-regulated kinase (ERK1/2), which activates HSL by phosphorylation on Ser 600 ( 23 ). It has been suggested that c-Jun N-terminal kinase (JNK) could play a role in the regulation of lipolysis based on the fact that silencing of Jnk1 and Jnk2 accelerates basal lipolysis in mouse adipocytes ( 24 ).…”

Section: Analysis Of Mrna Levelsmentioning

confidence: 99%

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Effects of lipoic acid on lipolysis in 3T3-L1 adipocytes

Fernández‐Galilea

Pérez-Matute

Prieto-Hontoria

et al. 2012

Journal of Lipid Research

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This article is available online at http://www.jlr.org properties. In fact, LA is able to directly scavenge reactive oxygen species (ROS) and regenerate endogenous antioxidants, such as glutathione and vitamins E and C ( 1, 2 ). Moreover, several studies have described potential beneficial effects of LA on obesity and its associated comorbidities, such as insulin resistance, type 2 diabetes, or fatty liver diseases. Thus, in rodents LA has been shown to cause profound weight loss by reducing food intake and enhancing energy expenditure ( 3 ) as well as by inducing a reduction on intestinal sugar absorption ( 4 ). More recently, two clinical trials in humans reported that LA caused signifi cant reductions of body weight, body mass index, blood pressure, and abdominal circumference in obese subjects ( 5, 6 ). LA also improved insulin sensitivity and plasma lipid profi le possibly through amelioration of oxidative stress and chronic infl ammatory status in obese patients with impaired glucose tolerance ( 7 ). Previous studies have provided strong evidence that LA is able to deeply affect adipose tissue development and function by the inhibition of adipogenesis ( 8 ), the regulation of the secretion of several adipokines such as leptin ( 9 ) and apelin ( 10 ), and by the promotion of mitochondrial biogenesis ( 11 ).In this context, previous studies suggested that LA seems to stimulate the lipolytic response in an in vitro model of broiler chicken adipocytes ( 12 ). However, the molecular mechanisms that mediate these effects remain unclear. Lipolysis is a complex process that is highly regulated and Lipoic acid (LA), or 1,2-dithiolane-3-pentaenoic acid, is a naturally occurring compound that contains two thiol groups with diverse benefi cial effects on health. The biological effects of LA were primarily associated with its antioxidant This work was supported, in part,

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supporting

confidence: 84%

Section: Analysis Of Mrna Levelsmentioning

confidence: 99%

Effects of lipoic acid on lipolysis in 3T3-L1 adipocytes

Fernández‐Galilea

Pérez-Matute

Prieto-Hontoria

et al. 2012

Journal of Lipid Research

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“…UV-or arsenite-induced apoptosis of fibroblasts required both JNK1 and JNK2 (191,192). In addition, lipolysis in adipocytes was also regulated by JNK1 and JNK2 (193). The results of these studies suggest that the different JNKs can act in a concerted manner in some cell and stimulus contexts.…”

Section: Comparison Of Jnk1 and Jnk2 Functions In Vivomentioning

confidence: 76%

JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

Zeke

Misheva

Reményi

et al. 2016

Microbiol Mol Biol Rev

409

350

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SUMMARYThe c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range of abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, and embryonic development, via their impact on gene expression, cytoskeletal protein dynamics, and cell death/survival pathways. Although the JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple protein partners of JNKs underlying the diversity of actions. Here we review the current knowledge of JNK structure and isoforms as well as the partnerships of JNKs with a range of intracellular proteins. Many of these proteins are direct substrates of the JNKs. We analyzed almost 100 of these target proteins in detail within a framework of their classification based on their regulation by JNKs. Examples of these JNK substrates include a diverse assortment of nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic proteins involved in cytoskeleton regulation (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), cell membrane receptors (BMPR2), and mitochondrial proteins (Mcl1, Bim). In addition, because upstream signaling components impact JNK activity, we critically assessed the involvement of signaling scaffolds and the roles of feedback mechanisms in the JNK pathway. Despite a clarification of many regulatory events in JNK-dependent signaling during the past decade, many other structural and mechanistic insights are just beginning to be revealed. These advances open new opportunities to understand the role of JNK signaling in diverse physiological and pathophysiological states.

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“…by guest, on May 11, 2018 www.jlr.org Downloaded from metabolism in mouse adipocytes ( 43 ). Our recent study showed that JNK2, but not JNK1, mediates regulation of CIDEC expression by insulin in human adipocytes ( 23 ).…”

Section: Jnk2 Mediates Insulin-induced Upregulation Of Lipogenic Enzymentioning

confidence: 88%

A novel JNK2/SREBP-1c pathway involved in insulin-induced fatty acid synthesis in human adipocytes

Ito¹,

Nagasawa²,

Omae³

et al. 2013

Journal of Lipid Research

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cular disease, nonalcoholic steatohepatitis, nephropathy, and several types of cancer ( 1-3 ). WAT mass is determined by the number and size of adipocytes ( 4, 5 ) regulated by cell differentiation, apoptosis, and lipid droplet (LD) formation (6)(7)(8). Insulin is known to inhibit apoptosis ( 9, 10 ) and increase LD formation ( 11,12 ) in adipocytes. Hyperinsulinemia is associated with weight gain in humans ( 13 ). Insulin signaling in adipocytes is critical for the development of obesity ( 14,15 ). Therefore, it has been suggested that insulin is one of the determinants involved in increasing the WAT mass.Our previous study showed that insulin decreases cell death-inducing DNA fragmentation factor-␣ -like effector (CIDE)A expression and increases CIDEC expression, both of which belong to the CIDE family and play critical roles in apoptosis ( 16,17 ) and LD formation ( 18-21 ), and the differential regulation of these genes is related, at least in part, to insulin-induced anti-apoptosis and LD formation in human adipocytes ( 22 ). Our recent study also showed that insulin regulates CIDEA and CIDEC expression via phosphatidylinositol 3-kinase (PI3K), and regulates expression of each protein via Akt1/2-and c-Jun N-terminal kinase (JNK)2-dependent pathways downstream of PI3K, respectively ( 23 ). These results suggest that insulin regulation of CIDEA and CIDEC contribute separately via different signaling pathways to insulin-induced antiapoptosis and LD formation, leading to increases in the number and size of adipocytes. Adipocyte size is determined by LD formation regulated by glucose uptake, de novo fatty acid synthesis, triacylglycerol synthesis, and lipolysis ( 24,25 ). Previous studies suggested that regulation of CIDEC expression contributes to LD maintenance by modulating lipolysis. However, regulation of other genes Press, March 19, 2013 DOI 10.1194 A novel JNK2/SREBP-1c pathway involved in insulininduced fatty acid synthesis in human adipocytes Abbreviations: ACC1, acetyl-CoA carboxylase 1; ACLY, ATP citrate lyase; CIDE, cell death-inducing DNA fragmentation factor-␣ -like effector; DAPI, 4 ′ ,6 ′ -diamidino-2-phenylindole; Dex, dexamethasone; FAS, fatty acid synthase; IPA, Ingenuity Pathway Analysis; JNK, c-Jun N-terminal kinase; LD, lipid droplet; n-SREBP-1c , nuclear form of sterol regulatory element binding protein-1c; PI3K, phosphatidylinositol 3-kinase; pre-SREBP-1c, precursor form of sterol regulatory element binding protein-1c; siJNK, JNK siRNA; siRNA, small interfering RNA; siSREBP-1, SREBP-1 siRNA; SREBP, sterol regulatory element binding protein; WAT, white adipose tissue. Published, JLR Papers in

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Silencing Jnk1 and Jnk2 accelerates basal lipolysis and promotes fatty acid re-esterification in mouse adipocytes

Cited by 23 publications

References 43 publications

Effects of lipoic acid on lipolysis in 3T3-L1 adipocytes

Effects of lipoic acid on lipolysis in 3T3-L1 adipocytes

JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

A novel JNK2/SREBP-1c pathway involved in insulin-induced fatty acid synthesis in human adipocytes

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