Expression analysis of a cholecystokinin system in human and rat white adipose tissue

Plaza, Adrián; Merino, Beatriz; Sánchez‐Pernaute, Andrés; Torres-García, Antonio José; Rubio, Miguel A.; Ruiz‐Gayo, Mariano

doi:10.1016/j.lfs.2018.05.036

Cited by 6 publications

(16 citation statements)

References 33 publications

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“…Moreover, CCK‐8 effects appeared to be insulin‐dependent and, in the case of subcutaneous WAT, linked to the activation of PPARγ. Taken together, our findings support the concept, already suggested by previous studies carried out by our group and others (King, Yang, Huesman, Rider, & Lo, ; Plaza, Merino, Cano, et al, ; Plaza, Merino, Sánchez‐Pernaute, et al, ), that both CCK and CCK binding sites have a relevant role in modulating WAT homeostasis, particularly in the case of Sc‐WAT.…”

Section: Discussionsupporting

confidence: 92%

“…The finding that triciribine blocks the effect of CCK‐8 on adiponectin expression further confirms the importance of Akt in the CCK 2 receptor‐mediated responses in WAT (Plaza, Merino, Sánchez‐Pernaute, et al, ). The role of Akt in regulating adiponectin gene expression has not yet been fully elucidated, although Akt‐mediated phosphorylation of FoxO1 has been proposed to mediate the nuclear exclusion of this transcription factor.…”

Section: Discussionsupporting

confidence: 71%

“…The CCK 2 receptors (also previously called gastrin receptors) are widely expressed in the CNS (Dufresne, Seva, & Fourmy, ) and, in the periphery; these receptors play a major role in maintaining the normal function of gastric mucosa (Chen et al, ). A recent study carried out in our laboratory has shown that activation of CCK 2 receptors facilitates the uptake of dietary triglycerides by white adipocytes, suggesting that CCK is involved in regulating homeostasis in white adipose tissue (WAT) (Plaza, Merino, Cano, et al, ; Plaza, Merino, Sánchez‐Pernaute, et al, ). Related with that, studies carried out by Flatt's group have provided evidence of the effect of CCK in alleviating symptoms of insulin resistance (Irwin et al, ; Irwin, Montgomery, O'harte, Frizelle, & Flatt, ), which supports the concept of an insulin/CCK drive of energy metabolism.…”

Section: Introductionmentioning

confidence: 99%

“…Taking into account (a) the role of CCK in regulating WAT homeostasis (Plaza, Merino, Cano, et al, ), (b) the existence of a complete CCK system in WAT (Plaza, Merino, Sánchez‐Pernaute, et al, ), and (c) the already reported interaction between CCK and insulin in driving energy metabolism (Irwin et al, ; Irwin et al, ; Pathak, Flatt, & Irwin, ), we aimed at investigating the effect of the C‐terminal bioactive fragment of CCK, CCK‐8, on both adiponectin gene ( Adipoq ) expression and adiponectin production in rat WAT.…”

Section: Introductionmentioning

confidence: 99%

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The cholecystokinin receptor agonist, CCK‐8, induces adiponectin production in rat white adipose tissue

Plaza

Merino

Olmo

et al. 2019

British J Pharmacology

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Background and Purpose:A cholecystokinin (CCK) system has been identified in white adipose tissue (WAT). Nevertheless, the endocrine actions of CCK on WAT remain unknown. Our goal was to investigate the role of CCK in regulating the production of adiponectin, an adipokine expressed in WAT, which is pivotal in preserving energy homeostasis. Experimental Approach:The effect of the bioactive CCK fragment CCK-8 on adiponectin production was studied both in vivo and in vitro. CCK-8 effects were characterized in rats treated with selective CCK 1 and CCK 2 receptor antagonists as well as in pre-adipocytes carrying the selective silencing of either CCK 1 or CCK 2 receptors. The influence of insulin on CCK-8 responses was also analysed. Key Results: In WAT, CCK-8 increased plasma adiponectin levels and the expression of the adiponectin gene (Adipoq). In pre-adipocytes, CCK-8 up-regulated adiponectin production. CCK-8 effects were abolished by L-365,260, a selective CCK 2 receptor antagonist. CCK 2 receptor knockdown also abolished the effects of CCK-8 in pre-adipocytes. Moreover, in vitro CCK-8 effects were blocked by triciribine, a specific inhibitor of protein kinase B (Akt) and by the PPARγ antagonist T0070907. Silencing the expression of the insulin receptor inhibited CCK-8-induced Adipoq expression in pre-adipocytes. Furthermore, insulin potentiated the effect of CCK-8. Conclusion and Implications: CCK-8 stimulates adiponectin production in WAT by acting on CCK 2 receptors, through a mechanism involving both Akt and PPARγ. Moreover, CCK-8 actions are only observed in the presence of insulin. Our results could have translational value in the design of new insulin-sensitizing therapies.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The cholecystokinin receptor agonist, CCK‐8, induces adiponectin production in rat white adipose tissue

Plaza

Merino

Olmo

et al. 2019

British J Pharmacology

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“…Animal studies are reported in compliance with the ARRIVE guidelines (Percie du Sert et al, 2020) and with the recommendations made by the British Journal of Pharmacology (Lilley et al, 2020). In vivo assays were performed in 12‐ to 14‐week‐old male Sprague–Dawley rats (Merino, Cano, et al, 2008; Merino, Somoza, et al, 2008; Plaza, Merino, Sánchez‐Pernaute, et al, 2018).…”

Section: Methodsmentioning

confidence: 99%

Cholecystokinin promotes functional expression of the aquaglycerol channel aquaporin 7 in adipocytes

Plaza

Merino

Ruiz‐Gayo

2022

British J Pharmacology

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Background and Purpose Cholecystokinin (CCK) promotes triglyceride storage and adiponectin production in white adipose tissue (WAT), suggesting that CCK modulates WAT homeostasis. Our goal was to investigate the role of CCK in regulating the expression and function of the aquaglycerol channel aquaporin 7 (AQP7), a protein that is pivotal for maintaining adipocyte homeostasis and preserving insulin responsiveness. Experimental Approach The effect of the bioactive fragment of CCK, CCK‐8, in regulating adipose AQP7 expression and glycerol efflux was assessed in rats as well as in preadipocytes. Moreover, the involvement of insulin receptors in the effects of CCK‐8 was characterized in preadipocytes lacking insulin receptors. Key Results CCK‐8 induced AQP7 gene expression in rat WAT, concomitantly increasing plasma glycerol concentration. In isolated preadipocytes, CCK‐8 also enhanced both AQP7 expression and glycerol leakage. The effects of CCK‐8 were independent of the lipolysis rate, as CCK‐8 failed to promote fatty acid release by adipocytes. In addition, CCK‐8 did not enhance hormone sensitive lipase phosphorylation, which is the rate‐limiting step of lipolysis. Moreover, the effects of CCK‐8 were dependent on the activation of protein kinase B and PPARγ. Silencing insulin receptor expression inhibited CCK‐8‐induced Aqp7 expression in preadipocytes. Furthermore, insulin enhanced the effect of CCK‐8. Conclusions and Implications CCK regulates AQP7 expression and function, and this effect is dependent on insulin. Accordingly, CCK receptor agonists could be suitable for preserving and improving insulin responsiveness in WAT.

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Identification of genetic variants the CCKAR gene and based on body measurement and carcass quality characteristics in Qinchuan beef cattle (Bos taurus)

Kaster

Raza

Khan

et al. 2021

Electronic Journal of Biotechnology

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Expression analysis of a cholecystokinin system in human and rat white adipose tissue

Cited by 6 publications

References 33 publications

The cholecystokinin receptor agonist, CCK‐8, induces adiponectin production in rat white adipose tissue

The cholecystokinin receptor agonist, CCK‐8, induces adiponectin production in rat white adipose tissue

Cholecystokinin promotes functional expression of the aquaglycerol channel aquaporin 7 in adipocytes

Identification of genetic variants the CCKAR gene and based on body measurement and carcass quality characteristics in Qinchuan beef cattle (Bos taurus)

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