Cdc2-like kinase 2 in the hypothalamus is necessary to maintain energy homeostasis

Quaresma, Paula G.F.; Weissmann, Laís; Zanotto, Tamires M.; Santos, Andrey; Matos, Manuel Arlindo Amador de; Furigo, Isadora C.; Simabuco, Fernando Moreira; Donato, José; Bittencourt, Jackson C.; Lopes‐Cendes, Íscia; Prada, Patrícia O.

doi:10.1038/ijo.2016.174

Cited by 16 publications

(40 citation statements)

References 34 publications

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“…Recently, the stereotaxic injection of a viral vector has become an indispensable tool which allows scientists to functionally dissect the role of hormone and neural circuits in vivo 55 . Similar to previous reports, 21,56,57 we performed a stereotaxic injection of a viral vector for gene manipulation in the MBH to induce adult‐onset JAZF1 overexpression. However, an adenoviral injection in the MBH may cause inflammation which could complicate data interpretation.…”

Section: Discussionmentioning

confidence: 88%

Effect of central JAZF1 on glucose production is regulated by the PI3K‐Akt‐AMPK pathway

Zhou

Wang

et al. 2020

FASEB j.

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The role of central juxtaposed with another zinc finger gene 1 (JAZF1) in glucose regulation remains unclear. Here, we activated mediobasal hypothalamus (MBH) JAZF1 in high-fat diet (HFD)-fed rats by an adenovirus expressing JAZF1 (Ad-JAZF1). We evaluated the changes in the hypothalamic insulin receptor (InsR)-PI3K-Akt-AMPK pathway and hepatic glucose production (HGP). To investigate the impact of MBH Ad-JAZF1 on HGP, we activated MBH JAZF1 in the presence or absence of ATPdependent potassium (K ATP ) channel inhibition, hepatic branch vagotomy (HVG), or an AMPK activator (AICAR). In HFD-fed rats, MBH Ad-JAZF1 decreased body weight and food intake, and inhibited HGP by increasing hepatic insulin signaling. Under insulin stimulation, MBH Ad-JAZF1 increased InsR and Akt phosphorylation, and phosphatidylinositol 3, 4, 5-trisphosphate (PIP3) formation; however, AMPK phosphorylation was decreased in the hypothalamus. The positive effect of MBH JAZF1 on hepatic insulin signaling and HGP was prevented by treatment with | 7059 ZHOU et al.

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Section: Discussionmentioning

confidence: 88%

Effect of central JAZF1 on glucose production is regulated by the PI3K‐Akt‐AMPK pathway

Zhou

Wang

et al. 2020

FASEB j.

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“…Overexpression of CLK2 in the mediobasal thalamus in mice on a high-fat diet can partially reverse the obese phenotype [ 110 ]. CLK2 regulates CREB via the attenuation of CREB inhibitory dephosphorylation by PP2Am, which affects diet-induced thermogenesis in brown adipose tissue via increased CREB-dependent expression of UCP1 [ 93 ].…”

Section: Effects Of Altered Clk Expressionmentioning

confidence: 99%

Cdc-Like Kinases (CLKs): Biology, Chemical Probes, and Therapeutic Potential

Moyano

Němec

Paruch

2020

IJMS

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Protein kinases represent a very pharmacologically attractive class of targets; however, some members of the family still remain rather unexplored. The biology and therapeutic potential of cdc-like kinases (CLKs) have been explored mainly over the last decade and the first CLK inhibitor, compound SM08502, entered clinical trials only recently. This review summarizes the biological roles and therapeutic potential of CLKs and their heretofore published small-molecule inhibitors, with a focus on the compounds’ potential to be utilized as quality chemical biology probes.

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“…Mice lacking this PKA subunit display reduced adiposity and resistance to DIO. Recently, Cdc2-like kinase 2 (CLK2) activity was proven to be regulated by leptin in a PI3K-dependent manner and reduction of CLK2 expression in the hypothalamus was sufficient to abolish the anorexigenic effect of leptin ( 163 ).…”

Section: Obr Signalingmentioning

confidence: 99%

The Leptin Receptor Complex: Heavier Than Expected?

2017

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Under normal physiological conditions, leptin and the leptin receptor (ObR) regulate the body weight by balancing food intake and energy expenditure. However, this adipocyte-derived hormone also directs peripheral processes, including immunity, reproduction, and bone metabolism. Leptin, therefore, can act as a metabolic switch connecting the body’s nutritional status to high energy consuming processes. We provide an extensive overview of current structural insights on the leptin–ObR interface and ObR activation, coupling to signaling pathways and their negative regulation, and leptin functioning under normal and pathophysiological conditions (obesity, autoimmunity, cancer, … ). We also discuss possible cross-talk with other receptor systems on the receptor (extracellular) and signaling cascade (intracellular) levels.

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Cdc2-like kinase 2 in the hypothalamus is necessary to maintain energy homeostasis

Abstract: Thus, our results suggest that protein CLK2 integrates some important hypothalamic pathways, and may be a promising molecule for new therapeutic approaches for obesity and diabetes.

Cited by 16 publications

References 34 publications

Effect of central JAZF1 on glucose production is regulated by the PI3K‐Akt‐AMPK pathway

Effect of central JAZF1 on glucose production is regulated by the PI3K‐Akt‐AMPK pathway

Cdc-Like Kinases (CLKs): Biology, Chemical Probes, and Therapeutic Potential

The Leptin Receptor Complex: Heavier Than Expected?

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