scholarly journals EFFECT OF MYOKINES ON THE QUANTITY OF HORMONE SENSITIVE LIPASE IN MSCS AND THE PRODUCTS OF THEIR ADIPOGENIC DIFFERENTIATION

Author(s):  
A. Mishra ◽  
E. V. Tsypandina ◽  
A. M. Gaponov ◽  
S. A. Rumyantsev ◽  
R. A. Khanferyan ◽  
...  

The basic metabolic process associated with white and beige/brown adipose tissues is lipolysis – the sequential enzymatic process of the hydrolysis of triglycerides in the adipose tissue. It has been repeatedly shown that physical activity activates lipolysis. It has recently been shown that skeletal muscles have an endocrine role; producing a host of myogenic hormones – myokines. Current literature has an incomplete understanding of the interdependent relationship between skeletal muscles and adipose tissue. We researched the influence of myocyte secreted cytokines (myokines) – meteorin-like protein (METRNL) and β-aminoisobutyric acid (BAIBA), and the adrenergic agonist isoproterenol on the levels of total and phosphorylated (Ser552) hormone sensitive lipase (HSL) in adipose tissue derived mesenchymal stromal cells (MSCs) and the cellular products of their adipogenic differentiation. The MSCs were obtained from 5 healthy donors. The adipogenic differentiation protocol was carried out for a span of 21 days. After procuring the adipocyte cultures, the following stimulators were added – 5 μM METRNL, 5 μM BAIBA, and 5 μM isoproterenol. With the help of western blot, the change in the amount of total and activated levels of HSL were monitored in cells of three different adipogenic differentiation protocols in MSCs. We observed that HSL and its activated form are produced in cell cultures induced with factors for white, beige, and brown adipogenic differentiation.

2019 ◽  
Vol 2019 (5) ◽  
Author(s):  
Stephen P.H. Alexander ◽  
Patrick Doherty ◽  
David Fairlie ◽  
Christopher J. Fowler ◽  
Christopher M. Overall ◽  
...  

Listed in this section are hydrolases not accumulated in other parts of the Concise Guide, such as monoacylglycerol lipase and acetylcholinesterase. Pancreatic lipase is the predominant mechanism of fat digestion in the alimentary system; its inhibition is associated with decreased fat absorption. CES1 is present at lower levels in the gut than CES2 (P23141), but predominates in the liver, where it is responsible for the hydrolysis of many aliphatic, aromatic and steroid esters. Hormone-sensitive lipase is also a relatively non-selective esterase associated with steroid ester hydrolysis and triglyceride metabolism, particularly in adipose tissue. Endothelial lipase is secreted from endothelial cells and regulates circulating cholesterol in high density lipoproteins.


2010 ◽  
Vol 299 (1) ◽  
pp. R140-R149 ◽  
Author(s):  
Y. B. Shrestha ◽  
C. H. Vaughan ◽  
B. J. Smith ◽  
C. K. Song ◽  
D. J. Baro ◽  
...  

Norepinephrine (NE) released from the sympathetic nerves innervating white adipose tissue (WAT) is the principal initiator of lipolysis in mammals. Central WAT sympathetic outflow neurons express melanocortin 4-receptor (MC4-R) mRNA. Single central injection of melanotan II (MTII; MC3/4-R agonist) nonuniformly increases WAT NE turnover (NETO), increases interscapular brown adipose tissue (IBAT) NETO, and increases the circulating lipolytic products glycerol and free fatty acid. The WAT pads that contributed to this lipolysis were inferred from the increases in NETO. Because phosphorylation of perilipin A (p-perilipin A) and hormone-sensitive lipase are necessary for NE-triggered lipolysis, we tested whether MTII would increase these intracellular markers of lipolysis. Male Siberian hamsters received a single 3rd ventricular injection of MTII or saline. Trunk blood was collected at 0.5, 1.0, and 2.0 h postinjection from excised inguinal, retroperitoneal, and epididymal WAT (IWAT, RWAT, and EWAT, respectively) and IBAT pads. MTII increased circulating glycerol concentrations at 0.5 and 1.0 h, whereas free fatty acid concentrations were increased at 1.0 and 2.0 h. Western blot analysis showed that MTII specifically increased p-perilipin A and hormone-sensitive lipase only in fat pads that previously had MTII-induced increases in NETO. Phosphorylation increased in IWAT at all time points and IBAT at 0.5 h, but not RWAT or EWAT at any time point. These results show for the first time in rodents that p-perilipin A can serve as an in vivo, fat pad-specific indictor of lipolysis and extend our previous findings showing that central melanocortin stimulation increases WAT lipolysis.


1997 ◽  
Vol 328 (1) ◽  
pp. 137-143 ◽  
Author(s):  
Henrik LAURELL ◽  
Jacques GROBER ◽  
Cécile VINDIS ◽  
Thierry LACOMBE ◽  
Michèle DAUZATS ◽  
...  

Hormone-sensitive lipase (HSL) catalyses the rate-limiting step of adipose tissue lipolysis. The enzyme is also expressed in steroidogenic tissues, mammary gland, muscle tissues and macrophages. A novel HSL mRNA termed hHSL-S, 228 bp shorter than the full-length HSL mRNA, was detected in human adipocytes. hHSL-S mRNA results from the in-frame skipping of exon 6, which encodes the serine residue of the catalytic triad. The corresponding 80 kDa protein was identified in human adipocytes after immunoprecipitation. The truncated protein expressed in COS cells showed neither lipase nor esterase activity but was phosphorylated by cAMP-dependent protein kinase. hHSL-S mRNA was found in all human tissues expressing HSL, except brown adipose tissue from newborns. It represented approx. 20% of total HSL transcripts in human subcutaneous adipocytes. No alternative splicing was detected in other mammals. Human and mouse three-exon HSL minigenes transfected into primate and rodent cell lines reproduced the splicing pattern of the endogenous HSL genes. Analysis of hybrid human/mouse minigenes transfected into human cell lines showed that cis-acting elements responsible for the skipping of human exon 6 were restricted to a 247 bp region including exon 6 and the first 19 nt of intron 6. Moreover, divergence in exonic splicing elements between mouse and human was shown to be critical for the species-specific alternative splicing.


Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 395 ◽  
Author(s):  
Xiao Zhang ◽  
Cong Cong Zhang ◽  
Hao Yang ◽  
Krishnakant G. Soni ◽  
Shu Pei Wang ◽  
...  

White adipose tissue (WAT) lipolysis contributes to energy balance during fasting. Lipolysis can proceed by the sequential hydrolysis of triglycerides (TGs) by adipose triglyceride lipase (ATGL), then of diacylglycerols (DGs) by hormone-sensitive lipase (HSL). We showed that the combined genetic deficiency of ATGL and HSL in mouse adipose tissue produces a striking different phenotype from that of isolated ATGL deficiency, inconsistent with the linear model of lipolysis. We hypothesized that the mechanism might be functional redundancy between ATGL and HSL. To test this, the TG hydrolase activity of HSL was measured in WAT. HSL showed TG hydrolase activity. Then, to test ATGL for activity towards DGs, radiolabeled DGs were incubated with HSL-deficient lipid droplet fractions. The content of TG increased, suggesting DG-to-TG synthesis rather than DG hydrolysis. TG synthesis was abolished by a specific ATGL inhibitor, suggesting that ATGL functions as a transacylase when HSL is deficient, transferring an acyl group from one DG to another, forming a TG plus a monoglyceride (MG) that could be hydrolyzed by monoglyceride lipase. These results reveal a previously unknown physiological redundancy between ATGL and HSL, a mechanism for the epistatic interaction between Pnpla2 and Lipe. It provides an alternative lipolytic pathway, potentially important in patients with deficient lipolysis.


1987 ◽  
Vol 7 (11) ◽  
pp. 897-904 ◽  
Author(s):  
Cecilia Holm ◽  
Gudrun Fredrikson ◽  
Barbara Cannon ◽  
Per Belfrage

Hormone-sensitive lipase (HSL) in brown adipose tissue from mice was identified through immunoprecipitation with a polyclonal antibody (anti-HSL) towards rat white fat HSL and Western blotting. An 82 kDa polypeptide, slightly smaller than the rat white fat HSL 84 kDa subunit, was detected and its identity as HSL verified by inhibition properties. The HSL concentration per g tissue was several-fold higher in the mouse brown adipose tissue than in the rat white adipose tissue, but the specific activities per mg protein were similar. Cold-exposure (4°C of the mice for 24 h approximately doubled the HSL concentration but this increase parallelled the overall protein increase and did not reflect a specific effect on the HSL.


2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Stephen P.H. Alexander ◽  
Patrick Doherty ◽  
David Fairlie ◽  
Christopher J. Fowler ◽  
Christopher M. Overall ◽  
...  

Listed in this section are hydrolases not accumulated in other parts of the Concise Guide, such as monoacylglycerol lipase and acetylcholinesterase. Pancreatic lipase is the predominant mechanism of fat digestion in the alimentary system; its inhibition is associated with decreased fat absorption. CES1 is present at lower levels in the gut than CES2 (P23141), but predominates in the liver, where it is responsible for the hydrolysis of many aliphatic, aromatic and steroid esters. Hormone-sensitive lipase is also a relatively non-selective esterase associated with steroid ester hydrolysis and triglyceride metabolism, particularly in adipose tissue. Endothelial lipase is secreted from endothelial cells and regulates circulating cholesterol in high density lipoproteins.


2018 ◽  
Vol 64 (4) ◽  
pp. 244-251
Author(s):  
Natalia B. Chagay ◽  
Ashot M. Mkrtumyan

Methylation of catechol estrogens is catalyzed by catechol-O-methyltransferase. Synthesis and activity of this enzyme is encoded by the COMT gene. Downregulation of COMT expression is responsible for the risk of developing estrogen-dependent tumors. Obesity is a factor determining the overall methylation status in the body. There are two main types of adipose tissue differing in their functional and metabolic characteristics, as well as the microscopic structure: white adipose tissue (WAT) and brown adipose tissue (BAT). Lipolysis of WAT is controlled by hormone-sensitive lipase, which depends is catecholamine dependent. BAT is a special type of adipose tissue whose main function is to produce heat. Activation of β3-adrenergic receptors by catecholamines, both at the central and peripheral levels, is the primary mechanism regulating thermogenesis in mature BAT. Obese patients develop adipose tissue hypoxia, as well as WAT and BAT dysfunction. Adrenergic stimulation of thermogenesis is unclaimed because of «whitening» of brown adipocytes, which manifests itself as degradation of mitochondria. Redirection of stimulation of hormone-sensitive lipase by catecholamines to WAT and the increased need to enhance COMT expression are the potential consequences of modifying the BAT metabolism. Estrogens are natural modulators of lipolysis (as they selectively affect activity of hormone-sensitive lipase) and regulators of BAT thermogenesis. Obesity is accompanied by elevated synthesis of estrone. However, in postmenopausal women it is characterized by a decrease in the total mass and activity of BAT. The role of BAT in the progression or inhibition of growth of the estrogen-dependent tumor tissue at premenopausal and postmenopausal age has not been studied yet and is of interest to researchers. The possible correlation between the activity of brown adipocytes and the COMT expression level is discussed in the context of the risk of developing benign breast dysplasia and cancer.


1981 ◽  
Vol 256 (12) ◽  
pp. 6311-6320
Author(s):  
G. Fredrikson ◽  
P. Strålfors ◽  
N.O. Nilsson ◽  
P. Belfrage

1998 ◽  
Vol 83 (2) ◽  
pp. 626-631 ◽  
Author(s):  
Jaswinder S. Samra ◽  
Mo L. Clark ◽  
Sandy M. Humphreys ◽  
Ian A. MacDonald ◽  
Peter A. Bannister ◽  
...  

Cortisol is known to increase whole body lipolysis, yet chronic hypercortisolemia results in increased fat mass. The main aim of the study was to explain these two apparently opposed observations by examining the acute effects of hypercortisolemia on lipolysis in subcutaneous adipose tissue and in the whole body. Six healthy subjects were studied on two occasions. On one occasion hydrocortisone sodium succinate was infused iv to induce hypercortisolemia (mean plasma cortisol concentrations, 1500 ± 100 vs. 335± 25 nmol/L; P < 0.001); on the other occasion (control study) no intervention was made. Lipolysis in the sc adipose tissue of the anterior abdominal wall was studied by measurement of arterio-venous differences, and lipolysis in the whole body was studied by constant infusion of[ 1,2,3-2H5]glycerol for measurement of the systemic glycerol appearance rate. Hypercortisolemia led to significantly increased arterialized plasma nonesterified fatty acid (NEFA; P < 0.01) and blood glycerol concentrations (P < 0.05), with an increase in systemic glycerol appearance (P < 0.05). However, in sc abdominal adipose tissue, hypercortisolemia decreased veno-arterialized differences for NEFA (P < 0.05) and reduced NEFA efflux (P < 0.05). This reduction was attributable to decreased intracellular lipolysis (P < 0.05), reflecting decreased hormone-sensitive lipase action in this adipose depot. Hypercortisolemia caused a reduction in arterialized plasma TAG concentrations (P < 0.05), but without a significant change in the local extraction of TAG (presumed to reflect the action of adipose tissue lipoprotein lipase). There was no significant difference in plasma insulin concentrations between the control and hypercortisolemia study. Site-specific regulation of the enzymes of intracellular lipolysis (hormone-sensitive lipase) and intravascular lipolysis (lipoprotein lipase) may explain the ability of acute cortisol treatment to increase systemic glycerol and NEFA appearance rates while chronically promoting net central fat deposition.


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