scholarly journals PKC and ERK mediate GH-stimulated lipolysis

2013 ◽  
Vol 51 (2) ◽  
pp. 213-224 ◽  
Author(s):  
Heather E Bergan ◽  
Jeffrey D Kittilson ◽  
Mark A Sheridan
Keyword(s):  
Molecular Mechanisms ◽  
De Novo ◽  
Hormone Sensitive Lipase ◽  
Akt Pathway ◽  
Lipolytic Enzyme ◽  
Erk Pathway ◽  
Physiological Processes ◽  
Kinase C ◽  
Hormone Sensitive ◽  
Growth Promoting

GH regulates several physiological processes in vertebrates, including the promotion of growth, an anabolic process, and the mobilization of stored lipids, a catabolic process. In this study, we used hepatocytes isolated from rainbow trout (Oncorhynchus mykiss) as a model to examine the mechanism of GH action on lipolysis. GH stimulated lipolysis as measured by increased glycerol release in both a time- and a concentration-related manner. The promotion of lipolysis was accompanied by GH-stimulated phosphorylation of the lipolytic enzyme hormone-sensitive lipase (HSL). GH-stimulated lipolysis was also manifested by an increased expression of the two HSL-encoding mRNAs, HSL1 and HSL2. The signaling pathways that underlie GH-stimulated lipolysis were also studied. GH resulted in the activation of phospholipase C (PLC)/protein kinase C (PKC) and the MEK/ERK pathway, whereas JAK–STAT and the PI3K–Akt pathway were deactivated. The blockade of PLC/PKC and the MEK/ERK pathway inhibited GH-stimulated lipolysis and GH-stimulated phosphorylation of HSL as well as GH-stimulated HSL mRNA expression, whereas the blockade of JAK–STAT or the PI3K–Akt pathway had no effect on the activation of lipolysis or the expression of HSL stimulated by GH. These results indicate that GH promotes lipolysis by activating HSL and by enhancing the de novo expression of HSL mRNAs via the activation of PKC and ERK. These findings also suggest molecular mechanisms for activating the lipid catabolic actions of GH while simultaneously deactivating anabolic processes such as antilipolysis and the growth-promoting actions of GH.

Molecular mechanisms regulating hormone-sensitive lipase and lipolysis

2003 ◽  
Vol 31 (6) ◽  
pp. 1120-1124 ◽  
Author(s):  
C. Holm
Keyword(s):  
Lipid Droplet ◽  
Molecular Mechanisms ◽  
Hormone Sensitive Lipase ◽  
Glucose Disposal ◽  
Triacylglycerol Lipase ◽  
Insulin Resistant ◽  
Lipolytic Action ◽  
Key Enzyme ◽  
Hormone Sensitive

HSL (hormone-sensitive lipase) is a key enzyme in the mobilization of fatty acids from acylglycerols in adipocytes as well as non-adipocytes. In adipocytes, catecholamines stimulate lipolysis mainly through PKA (protein kinase A)-mediated phosphorylation of HSL and perilipin, a protein coating the lipid droplet. The anti-lipolytic action of insulin is mediated mainly via lowered cAMP levels, accomplished through activation of phosphodiesterase 3B. Phosphorylation of HSL by PKA occurs at three sites, the serines 563, 659 and 660, both in vitro and in primary rat adipocytes. Phosphorylation of Ser-659 and -660 is required for in vitro activation as well as translocation from the cytosol to the lipid droplet, whereas the role of the third PKA site remains elusive. Adipocytes isolated from homozygous HSL-null mice, generated in our laboratory, exhibit completely blunted catecholamine-induced glycerol release and reduced fatty acid release, suggesting the presence of additional, although not necessarily hormone-activatable, triacylglycerol lipase(s). Basal hyperinsulinaemia, release of exaggerated amounts of insulin during glucose challenges and retarded glucose disposal during insulin tolerance tests suggest that HSL-null mice are insulin resistant. Liver, adipose tissue and skeletal muscle appear all to be sites of impaired insulin sensitivity in HSL-null mice.

scholarly journals Early signalling mechanism in colonic epithelial cell response to gastrin

1995 ◽  
Vol 311 (3) ◽  
pp. 945-950 ◽  
Author(s):  
R R Yassin ◽  
K M Little
Keyword(s):  
Tyrosine Phosphorylation ◽  
Molecular Mechanisms ◽  
Kinase Inhibitor ◽  
Tyrosine Phosphatase ◽  
Promoting Effect ◽  
Kinase C ◽  
Growth Promoting ◽  
Colonic Cells ◽  
Signalling Cascade ◽  
Isolation Buffer

The hormone gastrin exerts a growth-promoting effect on gastrointestinal cells. The molecular mechanisms by which colonic epithelial cells respond to gastrin are still poorly understood. In this study, we demonstrate a novel feature of the action of gastrin on normal colonic cells, namely the rapid phosphorylation on tyrosine of phospholipase C gamma 1 (PLC gamma 1). Tyrosine phosphorylation of PLC gamma 1, elicited by gastrin, was transient, concentration-dependent, and was abrogated by pretreating the colonic cells with the gastrin-receptor antagonist proglumide, the tyrosine kinase inhibitor genistein, and by removal of the tyrosine phosphatase inhibitor orthovanadate from the isolation buffer. Tyrosine phosphorylation of PLC gamma 1 correlated with the time- and concentration-dependent decrease in the mass of membrane phosphatidylinositol 4,5-bisphosphate (PIP2) and the increase in the epithelial concentration of inositol 1,4,5-trisphosphate (IP3). Likewise, the stimulated increase in IP3 was also prevented by proglumide and genistein. Gastrin induced a definite but transient increase in the intracellular concentration of free Ca2+ [Ca2+]i, and increased membrane-translocation of immunoreactive alpha- and beta-protein kinase C. The data thus indicate that gastrin elicits at least one signalling cascade, through rapid tyrosine phosphorylation of PLC gamma 1, leading to the activation of a PIP2-specific PLC pathway.

scholarly journals Molecular Mechanisms Underlying Sugarcane Response to Aluminum Stress by RNA-Seq

2020 ◽  
Vol 21 (21) ◽  
pp. 7934
Author(s):  
Thiago Mateus Rosa-Santos ◽  
Renan Gonçalves da Silva ◽  
Poornasree Kumar ◽  
Pratibha Kottapalli ◽  
Chiquito Crasto ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
De Novo ◽  
Transcriptome Assembly ◽  
Arable Land ◽  
Aluminum Tolerance ◽  
Aluminum Stress ◽  
Physiological Processes ◽  
Aluminum Ions ◽  
Detoxification Mechanism ◽  
Genomic Studies

Some metals are beneficial to plants and contribute to critical physiological processes. Some metals, however, are not. The presence of aluminum ions (Al3+) can be very toxic, especially in acidic soils. Considerable parts of the world’s arable land are acidic in nature; mechanistically elucidating a plant’s response to aluminum stress is critical to mitigating this stress and improving the quality of plants. To identify the genes involved in sugarcane response to aluminum stress, we generated 372 million paired-end RNA sequencing reads from the roots of CTC-2 and RB855453, which are two contrasting cultivars. Data normalization resulted in 162,161 contigs (contiguous sequences) and 97,335 genes from a de novo transcriptome assembly (trinity genes). A total of 4858 and 1307 differently expressed genes (DEGs) for treatment versus control were identified for the CTC-2 and RB855453 cultivars, respectively. The DEGs were annotated into 34 functional categories. The majority of the genes were upregulated in the CTC-2 (tolerant cultivar) and downregulated in RB855453 (sensitive cultivar). Here, we present the first root transcriptome of sugarcane under aluminum stress. The results and conclusions of this study are a crucial launch pad for future genetic and genomic studies of sugarcane. The transcriptome analysis shows that sugarcane tolerance to aluminum may be explained by an efficient detoxification mechanism combined with lateral root formation and activation of redox enzymes. We also present a hypothetical model for aluminum tolerance in the CTC-2 cultivar.

Function of hormone-sensitive lipase in diacylglycerol–protein kinase C pathway

2004 ◽  
Vol 65 (3) ◽  
pp. 209-215 ◽  
Author(s):  
Hideo Kanehara ◽  
Jinya Suzuki ◽  
Yasuo Zenimaru ◽  
Sadao Takahashi ◽  
Koji Oida ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Hormone Sensitive Lipase ◽  
Kinase C ◽  
Hormone Sensitive

Molecular mechanisms underlying regional variations of catecholamine-induced lipolysis in rat adipocytes

1995 ◽  
Vol 268 (6) ◽  
pp. E1135-E1142 ◽  
Author(s):  
G. Tavernier ◽  
J. Galitzky ◽  
P. Valet ◽  
A. Remaury ◽  
A. Bouloumie ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Subcutaneous Fat ◽  
Hormone Sensitive Lipase ◽  
Mrna Levels ◽  
Fat Depots ◽  
White Adipocytes ◽  
Adrenoceptor Agonists ◽  
Hormone Sensitive ◽  
Beta 2 ◽  
Fat Depot

The mechanisms underlying catecholamine control of lipolysis were studied in rat white adipocytes from epididymal, retroperitoneal, and subcutaneous fat depots. Sensitivity of subcutaneous adipocytes to selective beta 3-adrenoceptor agonists was lower than that of internal adipocytes. beta 3-Adrenoceptor mRNA levels were lower in subcutaneous adipocytes. A decreased beta 1/beta 2-adrenoceptor-mediated lipolysis was also observed in these adipocytes, and the number of beta 1/beta 2-adrenoceptors was lower than in the internal adipocytes. The number of alpha 2-adrenoceptors was higher in subcutaneous adipocytes without a marked difference in alpha 2-adrenoceptor-mediated antilipolysis between the depots. Subcutaneous adipocytes were also characterized by a lower maximal lipolytic response to drugs acting at different levels of the lipolytic cascade, suggesting differences at the postreceptor level. Lower hormone-sensitive lipase activity and mRNA levels in subcutaneous adipocytes were in agreement with the lipolysis data. These results suggest that the pattern of expression of the genes of the lipolytic pathway varies with the anatomic location of the fat depot.

scholarly journals Acetylation of Cavin-1 Promotes Lipolysis in White Adipose Tissue

2017 ◽  
Vol 37 (16) ◽  
Author(s):  
Shui-Rong Zhou ◽  
Liang Guo ◽  
Xu Wang ◽  
Yang Liu ◽  
Wan-Qiu Peng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Molecular Mechanisms ◽  
Hormone Sensitive Lipase ◽  
Dependent Manner ◽  
Nutritional Regulation ◽  
Fat Mobilization ◽  
Hormone Sensitive ◽  
Shed Light

ABSTRACT White adipose tissue (WAT) serves as a reversible energy storage depot in the form of lipids in response to nutritional status. Cavin-1, an essential component in the biogenesis of caveolae, is a positive regulator of lipolysis in adipocytes. However, molecular mechanisms of cavin-1 in the modulation of lipolysis remain poorly understood. Here, we showed that cavin-1 was acetylated at lysines 291, 293, and 298 (3K), which were under nutritional regulation in WAT. We further identified GCN5 as the acetyltransferase and Sirt1 as the deacetylase of cavin-1. Acetylation-mimetic 3Q mutants of cavin-1 augmented fat mobilization in 3T3-L1 adipocytes and zebrafish. Mechanistically, acetylated cavin-1 preferentially interacted with hormone-sensitive lipase and recruited it to the caveolae, thereby promoting lipolysis. Our findings shed light on the essential role of cavin-1 in regulating lipolysis in an acetylation-dependent manner in WAT.

scholarly journals Reducing 14-3-3ζ expression influences adipocyte maturity and impairs function

2020 ◽  
Author(s):  
Abel K. Oppong ◽  
Kadidia Diallo ◽  
Isabelle Robillard Frayne ◽  
Christine Des Rosiers ◽  
Gareth E. Lim
Keyword(s):  
Binding Sites ◽  
De Novo ◽  
Hormone Sensitive Lipase ◽  
Lipolytic Enzyme ◽  
Molecular Scaffolds ◽  
Mature Adipocyte ◽  
Metabolic Functions ◽  
Negative Effect ◽  
Subsequent Activation ◽  
The Impact

AbstractOne of the primary metabolic functions of a mature adipocyte is to supply energy via lipolysis, or the catabolism of stored lipids. Hormone-sensitive lipase (HSL) is a critical lipolytic enzyme, and its phosphorylation and subsequent activation by PKA generates phospho-binding sites for 14-3-3 proteins, a ubiquitously expressed family of molecular scaffolds. While we previously identified essential roles of the 14-3-3ζ isoform in murine adipogenesis, the presence of 14-3-3 protein binding sites on HSL suggests that 14-3-3ζ could also influence mature adipocyte processes like lipolysis. Herein, we demonstrate that 14-3-3ζ is necessary for lipolysis in male mice and fully differentiated 3T3-L1 adipocytes, as depletion of 14-3-3ζ significantly impaired glycerol and FFA release. Unexpectedly, this was not due to impairments in signaling events underlying lipolysis; instead, reducing 14-3-3ζ expression was found to significantly impact adipocyte maturity, as observed by reduced abundance of PPARγ2 protein and expression of mature adipocytes genes and those associated with de novo triglyceride synthesis and lipolysis. The impact of 14-3-3ζ depletion on adipocyte maturity was further examined with untargeted lipidomics, which revealed that reductions in 14-3-3ζ abundance promoted the acquisition of a lipidomic signature that resembled undifferentiated, pre-adipocytes. Collectively, these findings reveal a novel aspect of 14-3-3ζ in adipocytes, as reducing 14-3-3ζ was found to have a negative effect on adipocyte maturity and adipocyte-specific processes like lipolysis.

Expression of a chimeric retroviral-lipase mRNA confers enhanced lipolysis in a hibernating mammal

2001 ◽  
Vol 281 (4) ◽  
pp. R1186-R1192 ◽  
Author(s):  
Vernon W. Bauer ◽  
Teresa L. Squire ◽  
Mark E. Lowe ◽  
Matthew T. Andrews
Keyword(s):  
Primary Source ◽  
Ground Squirrels ◽  
Hormone Sensitive Lipase ◽  
Lipolytic Enzyme ◽  
Spermophilus Tridecemlineatus ◽  
Triacylglycerol Lipase ◽  
Hormone Sensitive ◽  
Regulatory Properties ◽  
Hydrolysis Of ◽  
Carbohydrate Catabolism

Hibernating mammals can survive several months without feeding by limiting their carbohydrate catabolism and using triacylglycerols stored in white adipose tissue (WAT) as their primary source of fuel. Here we show that a lipolytic enzyme normally found in the gut, pancreatic triacylglycerol lipase (PTL), is expressed in WAT of hibernating 13-lined ground squirrels ( Spermophilus tridecemlineatus). PTL expressed in WAT is encoded by an unusual chimeric retroviral-PTL mRNA ∼500 bases longer than the predominant PTL message found in other ground squirrel tissues. Seasonal measurements detect the chimeric mRNA and PTL enzymatic activity in WAT before and during hibernation, with both showing their lowest observed levels 1 wk after hibernation concludes in mid-March. PTL is expressed in addition to hormone-sensitive lipase, the enzyme typically responsible for hydrolysis of triacylglycerols in WAT. Because of the distinct catalytic and regulatory properties of both enzymes, this dual-triacylglycerol lipase system provides a means by which the fuel requirements of hibernating 13-lined ground squirrels can be met without interruption.

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