scholarly journals Methylation of estrogens, obesity and breast cancer

2018 ◽  
Vol 64 (4) ◽  
pp. 244-251
Author(s):  
Natalia B. Chagay ◽  
Ashot M. Mkrtumyan
Keyword(s):  
Adipose Tissue ◽  
Methylation Status ◽  
The Body ◽  
Hormone Sensitive Lipase ◽  
Main Function ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes ◽  
Brown Adipose ◽  
Hormone Sensitive ◽  
Stimulation Of

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.

Seasonal changes in hormone-sensitive and lipoprotein lipase mRNA concentrations in marmot white adipose tissue

1992 ◽  
Vol 262 (2) ◽  
pp. R177-R181 ◽  
Author(s):  
B. E. Wilson ◽  
S. Deeb ◽  
G. L. Florant
Keyword(s):  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
White Adipose Tissue ◽  
Mass Gain ◽  
The Body ◽  
Hormone Sensitive Lipase ◽  
Marmota Flaviventris ◽  
Fasting Period ◽  
Hormone Sensitive ◽  
Clear Increase

White adipose tissue (WAT) and plasma samples were obtained from yellow-bellied marmots (Marmota flaviventris) throughout the year. Mean plasma triacylglycerol (TG), free fatty acids (FFAs), and glycerol were determined. There was a clear increase in FFAs and decrease in mean TG and glycerol during the hibernation period when animals were fasting, suggesting increased lipolysis. RNA was isolated from WAT biopsies at four times in the year: spring, summer, fall, and winter. There were significant changes in the relative levels of mRNA for lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) during the body mass cycle of the marmot. The relative levels of LPL mRNA are high during the mass gain phase of the year and that of HSL mRNA are high during the fasting period when endogenous lipid is utilized. These results suggest that the genes for LPL and HSL are regulated seasonally to control the adipose mass depot in marmots.

scholarly journals Interscapular brown adipose tissue denervation does not promote the oxidative activity of inguinal white adipose tissue in male mice

2018 ◽  
Vol 315 (5) ◽  
pp. E815-E824 ◽  
Author(s):  
Sébastien M. Labbé ◽  
Alexandre Caron ◽  
William T. Festuccia ◽  
Roger Lecomte ◽  
Denis Richard
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucose Uptake ◽  
White Adipose Tissue ◽  
Oxidative Activity ◽  
Substrate Uptake ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes ◽  
Apparent Lack ◽  
Brown Adipose

Brown adipose tissue (BAT) thermogenesis is a key controller of energy metabolism. In response to cold or other adrenergic stimuli, brown adipocytes increase their substrate uptake and oxidative activity while uncoupling ATP synthesis from the mitochondrial respiratory chain activity. Brown adipocytes are found in classic depots such as in the interscapular BAT (iBAT). They can also develop in white adipose tissue (WAT), such as in the inguinal WAT (iWAT), where their presence has been associated with metabolic improvements. We previously reported that the induction of oxidative metabolism in iWAT is low compared with that of iBAT, even after sustained adrenergic stimulation. One explanation to this apparent lack of thermogenic ability of iWAT is the presence of an active iBAT, which may prevent the full activation of iWAT. In this study, we evaluated whether iBAT denervation-induced browning of white fat enhanced the thermogenic activity of iWAT following cold acclimation, under beta-3 adrenergic stimulation (CL 316,243). Following a bilateral denervation of iBAT, we assessed energy balance, evaluated the oxidative activity of iBAT and iWAT using 11C-acetate, and quantified the dynamic glucose uptake of those tissues using 2-deoxy-2-[18F]- fluoro-d-glucose. Our results indicate that despite portraying marked browning and mildly enhanced glucose uptake, iWAT of cold-adapted mice does not exhibit significant oxidative activity following beta-3 adrenergic stimulation in the absence of a functional iBAT. The present results suggest that iWAT is not readily recruitable as a thermogenic organ even when functional iBAT is lacking.

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

2021 ◽  
Vol 10 (4) ◽  
pp. 29-35
Author(s):  
A. Mishra ◽  
E. V. Tsypandina ◽  
A. M. Gaponov ◽  
S. A. Rumyantsev ◽  
R. A. Khanferyan ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Skeletal Muscles ◽  
Adipogenic Differentiation ◽  
Hormone Sensitive Lipase ◽  
Adrenergic Agonist ◽  
Differentiation Protocol ◽  
Healthy Donors ◽  
Brown Adipose ◽  
Hormone Sensitive ◽  
Hydrolysis Of

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.

Glucocorticoids and regulation of brown adipose tissue in humans – physiological and pathophysiological considerations

2017 ◽  
Vol 86 (3) ◽  
pp. 227
Author(s):  
Aleksander Rajczewski ◽  
Magdalena Gibas-Dorna
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
The Body ◽  
Adrenergic Stimulation ◽  
Therapeutic Goals ◽  
Bat Activity ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Differentiation And Proliferation

This review discusses the effects of glucocorticoids (GCs) on brown adipose tissue (BAT) in the context of obesity prevention and therapy. Due to the unique expression of the uncoupling protein 1 (UCP1), BAT is capable of non‑shivering thermogenesis, also defined as a metabolic heat production, related to increased metabolic rate. All processes that contribute to an increase in activity and/or quantity of BAT are able to upturn metabolism, and thus enable the above therapeutic goals to be achieved. GCs may stimulate BAT differentiation and proliferation. In the case of differentiation, the opposite effect of GCs has been also described. Within white adipose tissue (WAT) GCs inhibit the formation of so called beige adipocytes that are functionally and morphologically similar to the adipocytes from BAT. The activity of GCs with concomitant inhibition of WAT browning is mediated by the induction of microRNA-27b (MIR27B) expression. GCs are responsible for the decline in BAT activity as the body ages. Depriving the body of an enzyme responsible for local reduction of cortisone into an active GC‑cortisol in BAT (11β‑hydroxysteroid dehydrogenase type 1; 11β‑HSD1) prevents the reduction of BAT activity. The effects of high doses of GCs on BAT generally depend on the exposure time. Prolonged elevation in GCs level decreases BAT activity. During adrenergic stimulation the effect of GCs on BAT is ambiguous, because both decrease and increase in activity has been described. A full understanding of the GCs impact on brown remodeling in WAT may reveal a discovery of a novel preventive and therapeutic strategies for obesity and possibly other metabolic disorders.

scholarly journals Systemic  -Adrenergic Stimulation of Thermogenesis Is Not Accompanied by Brown Adipose Tissue Activity in Humans

Diabetes ◽  
2012 ◽  
Vol 61 (12) ◽  
pp. 3106-3113 ◽  
Author(s):  
M. J. Vosselman ◽  
A. A. J. J. van der Lans ◽  
B. Brans ◽  
R. Wierts ◽  
M. A. van Baak ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Adrenergic Stimulation ◽  
Brown Adipose ◽  
Brown Adipose Tissue Activity ◽  
Stimulation Of

Endurance training changes in lipolytic responsiveness of obese adipose tissue

1998 ◽  
Vol 275 (6) ◽  
pp. E951-E956 ◽  
Author(s):  
I. De Glisezinski ◽  
F. Crampes ◽  
I. Harant ◽  
M. Berlan ◽  
J. Hejnova ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Physical Training ◽  
The Body ◽  
Hormone Sensitive Lipase ◽  
Aerobic Exercise Training ◽  
Adrenoceptor Agonist ◽  
Before And After ◽  
Hormone Sensitive ◽  
Obese Subjects

The aim of this study was to investigate the effect of aerobic exercise training on the lipolytic response of adipose tissue in obese subjects. Thirteen men (body mass index = 36.9 ± 1.3 kg/m2) were submitted to aerobic physical training on a cycloergometer (30–45 min, 4 days a wk) for 3 mo. Adipocyte sensitivity to the action of catecholamines and insulin was studied in vitro before and after training. Training induced a decrease in the percentage of fat mass ( P < 0.05) without changing the body weight. Basal lipolysis and hormone-sensitive lipase activity were significantly decreased after training ( P < 0.05). The lipolytic effects of epinephrine, isoprenaline (β-adrenoceptor agonist), and dobutamine (β1-adrenoceptor agonist) were significantly increased ( P < 0.05) but not those of procaterol (β2-adrenoceptor agonist). The antilipolytic effects of α2-adrenoceptor and insulin were significantly decreased ( P < 0.05). Lipolysis stimulation by agents acting at the postreceptor level was unchanged after training. In conclusion, aerobic physical training in obese male subjects modifies adipose tissue lipolysis through an enhancement of β-adrenergic response and a concomitant blunting of adipocyte antilipolytic activity.

Hormone-sensitive lipase-independent adipocyte lipolysis during β-adrenergic stimulation, fasting, and dietary fat loading

2004 ◽  
Vol 287 (2) ◽  
pp. E282-E288 ◽  
Author(s):  
Mélanie Fortier ◽  
Shu Pei Wang ◽  
Pascale Mauriège ◽  
Meriem Semache ◽  
Léandra Mfuma ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
White Adipose Tissue ◽  
Dietary Fat ◽  
Intraperitoneal Administration ◽  
Hormone Sensitive Lipase ◽  
Adrenergic Stimulation ◽  
Hormone Sensitive ◽  
Isolated Adipocytes

In white adipose tissue, lipolysis can occur by hormone-sensitive lipase (HSL)-dependent or HSL-independent pathways. To study HSL-independent lipolysis, we placed HSL-deficient mice in conditions of increased fatty acid flux: β-adrenergic stimulation, fasting, and dietary fat loading. Intraperitoneal administration of the β3-adrenergic agonist CL-316243 caused a greater increase in nonesterified fatty acid level in controls (0.33 ± 0.05 mmol/l) than in HSL−/− mice (0.12 ± 0.01 mmol/l, P < 0.01). Similarly, in isolated adipocytes, lipolytic response to CL-316243 was greatly reduced in HSL−/− mice compared with controls. Fasting for ≤48 h produced normal mobilization and oxidation of fatty acids in HSL−/− mice, as judged by similar values of respiratory quotient and oxygen consumption as in HSL+/+ controls. In isolated adipocytes, lipolysis in the absence of β-adrenergic stimulation was 1.9-fold greater in HSL−/− than in HSL+/+ cells ( P < 0.05), increasing to 6.5-fold after fasting ( P < 0.01). After 6 wk of a fat-rich diet containing 31.5% of energy as lipid, weight gain of HSL−/− mice was 4.4-fold less than in HSL+/+ mice ( P < 0.01), and total abdominal fat mass was 5.2-fold lower in HSL−/− than in HSL+/+ mice ( P < 0.01). In white adipose tissue, HSL is essential for normal acute β-adrenergic-stimulated lipolysis and permits normal triglyceride storage capacity in response to dietary fat loading. However, HSL-independent lipolysis can markedly increase during fasting, both in isolated adipocytes and in intact mice, and can mediate a normal flux of fatty acids during fasting.

scholarly journals NCLX prevents cell death during adrenergic activation of the brown adipose tissue

2018 ◽  
Author(s):  
Essam A. Assali ◽  
Anthony E. Jones ◽  
Michaela Veliova ◽  
Mahmoud Taha ◽  
Nathanael Miller ◽  
...  
Keyword(s):  
Cell Death ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Mitochondrial Permeability Transition ◽  
Core Body Temperature ◽  
Adrenergic Stimulation ◽  
Brown Adipose ◽  
Stimulation Of

AbstractA sharp increase in mitochondrial Ca2+ marks the activation of the brown adipose tissue (BAT) thermogenesis, yet the mechanisms preventing Ca2+ deleterious effects are poorly understood. Here, we show that adrenergic stimulation of BAT activates a PKA-dependent mitochondrial Ca2+ extrusion via the mitochondrial Na+/Ca2+ exchanger, NCLX. Adrenergic stimulation of NCLX-ablated brown adipocytes (BA) induces a profound mitochondrial Ca2+ overload and impaired uncoupled respiration. Core body temperature, PET imaging and VO2 measurements confirm a BAT specific thermogenic defect in NCLX-null mice.We show that mitochondrial Ca2+ overload induced by adrenergic stimulation of NCLX-null BAT, triggers the opening of the mitochondrial permeability transition pore (mPTP), leading to remarkable mitochondrial swelling, Cytochrome c release and cell death in BAT. However, treatment with mPTP inhibitors rescue mitochondrial respiratory function and thermogenesis in NCLX-null BA, in vitro and in vivo.Our findings identify a novel pathway enabling non-lethal mitochondrial Ca2+ elevation during adrenergic stimulation of uncoupled respiration. Deletion of NCLX transforms the adrenergic pathway responsible for the stimulation of thermogenesis into a death pathway.

scholarly journals Adrenergic stimulation of lipoprotein lipase gene expression in rat brown adipocytes differentiated in culture: mediation via β3- and α1-adrenergic receptors

1997 ◽  
Vol 321 (3) ◽  
pp. 759-767 ◽  
Author(s):  
Pertti KUUSELA ◽  
Stefan REHNMARK ◽  
Anders JACOBSSON ◽  
Barbara CANNON ◽  
Jan NEDERGAARD
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Direct Effect ◽  
Mrna Levels ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes ◽  
Brown Adipose ◽  
Lpl Gene

In order to investigate whether the positive effect of adrenergic stimulation on lipoprotein lipase (LPL) gene expression in brown adipose tissue is a direct effect on the brown adipocytes themselves, the expression of the LPL gene was investigated by measuring LPL mRNA levels in brown adipocytes, isolated as precursors from the brown adipose tissue of rats and grown in culture in a fully defined medium before experimentation. Addition of noradrenaline led to an enhancement of LPL gene expression; the mRNA levels increased as a linear function of time for at least 5 h and were finally approx. 3 times higher than in control cells, an increase commensurate with that seen in vivoin both LPL mRNA levels and LPL activity during physiological stimulation. The increase was dependent on transcription. The effect of noradrenaline showed simple MichaelisŐMenten kinetics with an EC50 of approx. 11 nM. β3-Agonists (BRL-37344 and CGP-12177) could mimic the effect of noradrenaline; the β1-agonist dobutamine and the β2-agonist salbutamol could not; the α1-agonist cirazoline had only a weak effect. The effect of noradrenaline was fully inhibited by the β-antagonist propranolol and was halved by the α1-antagonist prazosin; the α2-antagonist yohimbine was without effect. An increase in LPL mRNA level similar to (but not significantly exceeding) that caused by noradrenaline could also be induced by the cAMP-elevating agents forskolin and cholera toxin, and 8-Br-cAMP also increased LPL mRNA levels. The increase in LPL gene expression was not mediated via an increase in the level of an intermediary proteinaceous factor. It is concluded that the physiologically induced increase in LPL gene expression is a direct effect of noradrenaline on the brown adipocytes themselves, mediated via a dominant β3-adrenergic pathway and an auxillary α1-adrenergic pathway which converge at a regulatory point in transcriptional control.

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