Vascular Peptide Endothelin-1 Links Fat Accumulation With Alterations of Visceral Adipocyte Lipolysis

Harmelen, Vanessa van; Eriksson, Anna; Åström, Gaby; Wåhlén, Kerstin; Näslund, Erik; Karpe, Fredrik; Frayn, Keith N.; Olsson, Tommy; Andersson, Jonas; Rydén, Mikael; Arner, Peter

doi:10.2337/db07-0893

Cited by 75 publications

(70 citation statements)

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“…In this study, we show that a similar albeit smaller effect is observed in human fat cells. This effect is only observed after 24 h. Incubations with receptor-specific agonists suggest that the lipolytic effect of ET-1 is mediated through the ET A R. It has earlier been shown that ET-1 inhibits the antilipolytic effect of insulin after long-term treatment of visceral adipocytes through the selective activation of ET B R. 10 Taken together, these results demonstrate that ET-1 can affect lipolytic regulation at several levels and through activation of different receptors. Earlier studies have shown that circulatory levels of ET-1 are increased in obesity.…”

Section: Discussionmentioning

confidence: 52%

“…10,[20][21][22][23][24] We have recently shown that s.c. adipose tissue, which is the major adipose region, might contribute to the elevated levels of ET-1 in the obese state. 10 This study shows that the expression of ET-1 mRNA is higher in s.c. adipose tissue compared with OM adipose tissue, whereas ETR expression is similar in the two depots . Expression analysis in cells from the different compartments in s.c. adipose tissue suggests that the major cellular source of ET-1 is present in the stroma vascular portion, mostly constituting endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…10 This leads indirectly to increased lipolysis in OM cells because of the reduced antilipolytic effect of insulin. However, given the recent findings demonstrating a direct lipolytic effect of ET-1 on rodent adipocytes, we assessed whether ET-1 may have similar direct effects in human adipocytes.…”

Section: Lipolytic Effects Of Et-1 In Human Adipocytesmentioning

confidence: 99%

“…[6][7][8][9] Receptors for ET-1 are expressed not only in smooth muscle cells but also in adipocytes and a number of other tissues. 6,10 It has recently been shown that ET-1 is released by human subcutaneous (s.c.) adipose tissue and that its secretion is elevated in obesity. 10 Moreover, ET-1 attenuates the inhibiting effect of insulin on lipolysis in visceral but not s.c. fat cells.…”

Section: Introductionmentioning

confidence: 99%

“…6,10 It has recently been shown that ET-1 is released by human subcutaneous (s.c.) adipose tissue and that its secretion is elevated in obesity. 10 Moreover, ET-1 attenuates the inhibiting effect of insulin on lipolysis in visceral but not s.c. fat cells. ET-1 may therefore be a factor that increases lipolysis in visceral fat cells, thereby contributing to the development of insulin resistance in obesity.…”

Section: Introductionmentioning

confidence: 99%

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Endothelin-1 stimulates human adipocyte lipolysis through the ETA receptor

et al. 2008

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Objective: Levels of the vascular peptide endothelin-1 (ET-1) are significantly elevated in obesity. Adipose tissue-derived ET-1 attenuates insulin-mediated antilipolysis in human visceral adipocytes through the activation of the ET receptor B (ET B R), thereby linking ET-1 to insulin resistance. Whether ET-1 has direct effects on lipolysis in human adipocytes is not known. Research design and subjects: Endothelin-1 receptor (ETR) mRNA expression was determined by quatitative PCR in 130 nonobese and obese subjects. ET-1 mRNA in different adipose tissue regions was also assessed. ETR protein expression was analyzed by western blotting in 37 subjects. The effect of ET-1 on lipolysis was assessed in freshly isolated adipocytes and in vitro differentiated adipocytes from human donors. Results: Freshly isolated human adipocytes incubated with different concentrations of ET-1 showed no acute effect on lipolysis. In contrast, a 24 h incubation in primary cultures of human adipocytes resulted in a significant 50% increase in lipolysis. This effect was concentration dependent and could be mimicked by an agonist of the ET A receptor but not with a selective ET B R agonist. Adipocyte differentiation was not affected by any of the agonists. In subcutaneous (s.c.) adipose tissue from 19 nonobese and 18 obese subjects, the protein expression of ET A R was significantly higher in obese subjects whereas there was no difference in ET B R expression. Interestingly, the differences in protein expression were not observed at the mRNA level as ET A R expression was similar between lean and obese subjects. Conclusion: Long-term but not acute incubation of human adipocytes with ET-1 results in a significant increase in lipolysis. This appears to be mediated through the activation of ET A R, demonstrating a yet another receptor-specific effect of ET-1. In addition, the protein expression of ET A R is increased in s.c. adipose tissue in obesity, possibly through post-transcriptional mechanisms. An increased effect of ET-1 could be a mechanism that contributes to increased basal lipolysis in human obesity.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Lipolytic Effects Of Et-1 In Human Adipocytesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Endothelin-1 stimulates human adipocyte lipolysis through the ETA receptor

et al. 2008

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Current literature in diabetes

2008

Diabetes Metabolism Res

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of diabetes/metabolism. Each bibliography is divided into 26 sections: 1 Reviews; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6 Obesity; 7 Prediction and Prevention; 8 Intervention: a) General; b) Care; c) Drug Therapy; d)Economics; e) Gene therapy; f) Nursing; g) Nutrition; h) Surgery; i) Transplantation; 9 Pathology and Complications: a) General; b) Cardiovascular; c) Eye disease; d) Gestational and fetal; e) Neurological; f) Podiatrical; g) Renal; 10 Endocrinology & Metabolism; 11 Experimental Studies; 12 Diagnosis and Techniques. Within each section, articles are listed in alphabetical order with respect to author

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Chronic endothelin‐1 infusion causes adipocyte hyperplasia in rats

Lien¹,

Jiang²,

Jian³

et al. 2016

Obesity

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Objective: The aim of this study was to investigate the regulatory mechanism of endothelin-1 (ET-1), an endothelium-derived vasoconstrictor, on adipogenesis in vitro and in vivo. Methods: 3T3-L1 preadipocytes were used to explore the mechanisms mediating ET-1 actions on preadipocyte proliferation and adipocyte differentiation. To investigate the in vivo effect of ET-1, male Sprague-Dawley rats were infused with ET-1 or saline for 4 weeks via intraperitoneally implanted osmotic pumps, and the fat pad weight and adipocyte size of adipose tissues were measured. Results: ET-1 stimulated preadipocyte proliferation and increased the cell number at the mitotic clonal expansion stage of adipocyte differentiation via the endothelin A receptor (ETAR) and activation of the protein kinase C (PKC) pathway. ET-1, via ETAR, inhibited adipocyte differentiation partially through an ERKdependent pathway. Furthermore, no significant difference in the body weight and fat pad weight was observed in either ET-1-or saline-infused rats. Compared with saline-infused rats, the adipocyte cell number was significantly increased but the adipocyte size was significantly decreased in ET-1-infused rats. Conclusions: Chronic ET-1 infusion increased the number of small adipocytes without the change of white adipose tissue mass in rats, which were associated with ET-1-stimulated preadipocyte proliferation, but not ET-1-suppressed adipocyte differentiation.

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Vascular Peptide Endothelin-1 Links Fat Accumulation With Alterations of Visceral Adipocyte Lipolysis

Cited by 75 publications

References 40 publications

Endothelin-1 stimulates human adipocyte lipolysis through the ETA receptor

Endothelin-1 stimulates human adipocyte lipolysis through the ETA receptor

Current literature in diabetes

Chronic endothelin‐1 infusion causes adipocyte hyperplasia in rats

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