Human fat cell beta-adrenergic receptors: beta-agonist-dependent lipolytic responses and characterization of beta-adrenergic binding sites on human fat cell membranes with highly selective beta 1-antagonists.

Mauriège, Pascale; Pergola, G. De; Berlan, Michel; Lafontan, Max

doi:10.1016/s0022-2275(20)38502-3

Cited by 109 publications

(8 citation statements)

References 37 publications

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“…Having demonstrated differences in the timing of isoproterenol- and IL-6-induced adipocyte lipolysis, we next pursued identification of other points of mechanistic divergence between these two lipolytic stimulants. It is well established that β-adrenergic induction of lipolysis is inhibited by the pan β-blocker propranolol ( 23 , 24 ). We have also previously shown that JAK inhibition suppresses IL-6 family cytokine-induced lipolysis in adipocytes ( 15 ).…”

Section: Resultsmentioning

confidence: 99%

Cytokine-Mediated STAT3 Transcription Supports ATGL/CGI-58-Dependent Adipocyte Lipolysis in Cancer Cachexia

Gandhi

Gupta

et al. 2022

Front. Oncol.

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Adipose tissue inflammation is observed in multiple metabolically-altered states including cancer-associated cachexia and obesity. Although cachexia is a syndrome of adipose loss and obesity is a disease of adipose excess, both pathologies demonstrate increases in circulating levels of IL-6 family cytokines, β-adrenergic signaling, and adipocyte lipolysis. While β-adrenergic-stimulated adipocyte lipolysis is well described, there is limited mechanistic insight into how cancer cachexia-associated inflammatory cytokines contribute to adipocyte lipolysis under pathologic conditions. Here, we set out to compare adipocyte lipolysis signaling by cancer cachexia-associated IL-6 family cytokines (IL-6 and LIF) to that of the β-adrenergic agonist isoproterenol. Unlike isoproterenol, the IL-6 family of cytokines required JAK/STAT3-dependent transcriptional changes to induce adipocyte lipolysis. Furthermore, cachexia-associated cytokines that used STAT3 to induce lipolysis were primarily dependent on the lipase ATGL and its cofactor CGI-58 rather than lipases HSL and MAGL. Finally, administration of JAK but not β-adrenergic inhibitors suppressed adipose STAT3 phosphorylation and associated adipose wasting in a murine model of cancer cachexia characterized by increased systemic IL-6 family cytokine levels. Combined, our results demonstrate how the IL-6 family of cytokines diverge from β-adrenergic signals by employing JAK/STAT3-driven transcriptional changes to promote adipocyte ATGL/CGI-58-dependent lipolysis contributing to adipose wasting in cancer cachexia.

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Section: Resultsmentioning

confidence: 99%

Cytokine-Mediated STAT3 Transcription Supports ATGL/CGI-58-Dependent Adipocyte Lipolysis in Cancer Cachexia

Gandhi

Gupta

et al. 2022

Front. Oncol.

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“…Beta 2 -adrenergic stimulation of white adipocytes Beta 2 -adrenergic receptors are widely expressed in human white adipose tissue, accounting for 40-90% of the transcripted beta-isoforms (Lafontan & Berlan, 1993;Reynisdottir et al 1994;Deng et al 1996;Blondin et al 2020) with a relative cell membrane concentration of 60-70% for the beta 2 -subtype vs. 30-40% for the beta 1 -subtype (Mauriege et al 1988;Lonnqvist et al 1992;Reynisdottir et al 1994). These values differ considerably between individuals and body regions (Arner et al 1990), and individuals with obesity, in particular, have a low abundance of the beta 2 -subtype and are less catecholamine sensitive (Lonnqvist et al 1992;Reynisdottir et al 1994).…”

Section: Beta 2 -Adrenergic Stimulation Of Brown Adipocytesmentioning

confidence: 99%

The beta₂‐adrenergic receptor – a re‐emerging target to combat obesity and induce leanness?

Hostrup

Onslev

2021

The Journal of Physiology

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His research focuses on the health-and performance-related benefits of exercise, performance optimization strategies and ergogenic substances. An extensive amount of his research has been devoted to beta 2 -agonist pharmacology with an emphasis on their effects in human skeletal muscle. Johan Onslev is a medical doctor at NEXS whose research interests include metabolism and endocrinology. He has published several papers on the effect of beta 2 -agonists on metabolism in humans.

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“…The lipolytic activity of the isolated fat cells was tested with epinephrine which is a mixed agonist ( ␣ 2/ ␤ ) with a higher affinity for ␣ 2-than for ␤ -adrenoceptor (AR) sites (17), UK-14304 (selective ␣ 2-AR agonist), isoproterenol (non selective ␤ -AR agonist) (19), procaterol ( ␤ 2-AR agonist), and dobutamine ( ␤ 1-AR agonist) (39,41). Ascorbic acid (0.1 mmol/l) was included in the incubation medium in order to prevent catecholamine degradation.…”

Section: Adipocyte Isolation and Lipolysismentioning

confidence: 99%

“…␣2as well as ␤-ARs were quantified with radioligands selective for each adrenergic receptor subtype, i.e., [ 3 H]RX 821002 (a more selective ␣2-AR antagonist than [ 3 H]yohimbine currently used) and 125 I-labeled cyanopindolol (CYP), a non-selective ␤-AR antagonist (39,41,45). Previous experiments have shown that radioligand binding assays were unaffected by the composition of the buffer (0.25 m sucrose, 1 mm EDTA, 1 mm dithiothreitol) used for adipose tissue membrane preparations (P. Mauriège, unpublished observations).…”

Section: Radioligand Binding Studiesmentioning

confidence: 99%

“…Briefly, membranes were incubated either with 5 nm of [ 3 H]-RX 821002 or with 300 pm of 125 I-labeled CYP for ␣2or the ␤-AR tracer experiments, respectively. As both radioligands bind to a single class of homogenous noninteracting binding sites that give straight lines on Scatchard analysis leading to Hill coefficients close to 1, the use of only one ligand concentration to determine maximal antagonist binding is therefore justified under such conditions (16,17,39,41). In addition, the latter concentrations corresponding to almost twice the affinity of each radioligand label the totality of both ARs (39,45).…”

Section: Radioligand Binding Studiesmentioning

confidence: 99%

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Regional and gender variations in adipose tissue lipolysis in response to weight loss

Mauriège

Imbeault

Langin

et al. 1999

Journal of Lipid Research

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Catecholamine-induced lipolysis was investigated in 32 obese subjects (14 men and 18 premenopausal women), aged 36-50 years, whose body mass index ranged from 30 to 42 kg/m 2 . Isolated subcutaneous (subc) abdominal and femoral adipocytes were studied before and after a 15-week weight reducing program, during which mean body weight loss averaged 9 vs. 10 kg in women and men, respectively ( P Ͻ 0.0001). Participants were re-examined when they were weight-stable. Fat cell weight decreased by about 15-20% in both depots ( P values ranging from 0.01 to 0.05). Epinephrine (mixed ␣ 2-/ ␤ -adrenoceptor (AR) agonist) induced antilipolysis at low concentrations and a net lipolytic response at higher doses, irrespective of subjects' fatness and anatomic location of fat. Basal lipolysis, maximal lipolytic responses to isoprenaline ( ␤ -AR agonist), dobutamine and procaterol ( ␤ 1-and ␤ 2-AR agonists, respectively) as well as maximal antilipolytic effects of epinephrine or UK-14304 ( ␣ 2-AR agonist) were similar before and after weight reduction. However, both ␤ -and ␤ 2-AR lipolytic sensitivities and the ␤ -AR density were increased in both genders after weight reduction, this effect being more marked in subc abdominal than in femoral adipocytes ( P values ranging from 0.001 to 0.05). The ␣ 2-AR antilipolytic sensitivity was reduced in adipose cells from both regions in women, but only in subc abdominal adipocytes in men ( P Ͻ 0.05), although the ␣ 2-AR density remained unchanged after weight reduction. In conclusion, a moderate weight loss leads to a higher adipose cell lipolytic efficiency which is associated with changes at receptor levels (mainly an increased ␤ 2-and a decreased ␣ 2-AR sensitivities), in both genders.

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Human fat cell beta-adrenergic receptors: beta-agonist-dependent lipolytic responses and characterization of beta-adrenergic binding sites on human fat cell membranes with highly selective beta 1-antagonists.

Cited by 109 publications

References 37 publications

Cytokine-Mediated STAT3 Transcription Supports ATGL/CGI-58-Dependent Adipocyte Lipolysis in Cancer Cachexia

Cytokine-Mediated STAT3 Transcription Supports ATGL/CGI-58-Dependent Adipocyte Lipolysis in Cancer Cachexia

The beta₂‐adrenergic receptor – a re‐emerging target to combat obesity and induce leanness?

Regional and gender variations in adipose tissue lipolysis in response to weight loss

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Human fat cell beta-adrenergic receptors: beta-agonist-dependent lipolytic responses and characterization of beta-adrenergic binding sites on human fat cell membranes with highly selective beta 1-antagonists.

Cited by 109 publications

References 37 publications

Cytokine-Mediated STAT3 Transcription Supports ATGL/CGI-58-Dependent Adipocyte Lipolysis in Cancer Cachexia

Cytokine-Mediated STAT3 Transcription Supports ATGL/CGI-58-Dependent Adipocyte Lipolysis in Cancer Cachexia

The beta2‐adrenergic receptor – a re‐emerging target to combat obesity and induce leanness?

Regional and gender variations in adipose tissue lipolysis in response to weight loss

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The beta₂‐adrenergic receptor – a re‐emerging target to combat obesity and induce leanness?