CDK7 Mediates the Beta-Adrenergic Signaling in Thermogenic Brown and White Adipose Tissues

Ji, Honglei; Chen, Yizhe; Castillo-Armengol, Judit; Dreos, René; Moret, Catherine; Niederhäuser, Guy; Delacuisine, Brigitte; López-Mejía, Isabel C.; Denechaud, Pierre-Damien; Fajas, Lluís

doi:10.1016/j.isci.2020.101163

Cited by 11 publications

(9 citation statements)

References 42 publications

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“…A first indication of the participation of CDK7 in WAT physiology came from the transcriptome data that we generated from perigonadal white adipose tissue (pgWAT) in CDK7 fat‐specific knockout mice (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE149128) [29]. Pathway analysis showed that a significant proportion of the 190 downregulated genes ( P < 0.05, log FC 0.5) that were found in the WAT of the Cdk7 aKO mice are involved in lipid metabolism (lipid synthesis, uptake and lipolysis) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The generation of Cdk7 flox/flox and Cdk7 aKO mice was reported in a previous study [29]. Mice were maintained in a temperature-controlled animal facility with a 12-h light/12-h dark cycle and had access to standard chow (KLIBA NAFAG, no.…”

Section: Micementioning

confidence: 99%

“…The differences were considered statistically significant at *P < 0.05, **P < 0.01 and ***P < 0.001. RNA-seq data from our previous study were analysed using METASCAPE [29,33]. All graphs were generated using GRAPHPAD PRISM 8.2.0 (San Diego, CA, USA).…”

Section: Statistical Analysesmentioning

confidence: 99%

“…We showed previously that CDK7 is required for beta‐adrenergic agonist‐induced adipose tissue browning [29], which points to an important function of this protein in adipose tissues. The role of CDK7 in white adipose tissue expansion under anabolic conditions, however, has not been reported.…”

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confidence: 99%

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Adipocyte‐specific CDK7 ablation leads to progressive loss of adipose tissue and metabolic dysfunction

et al. 2022

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Adipose tissue regulates whole‐body energy homeostasis. Both lipodystrophy and obesity, the extreme and opposite aspects of adipose tissue dysfunction, result in metabolic disorders: insulin resistance and hepatic steatosis. Cyclin‐dependent kinases (CDKs) have been reported to be involved in adipose tissue development and functions. Using adipose tissue‐specific knockout mice, here we demonstrate that the deletion of CDK7 in adipose tissue results in progressive lipodystrophy, insulin resistance, impaired adipokine secretion and downregulation of fat‐specific genes, which are aggravated on high‐fat diet and during ageing. Our studies suggest that CDK7 is a key regulatory component of adipose tissue maintenance and systemic energy homeostasis.

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Section: Resultsmentioning

confidence: 99%

Section: Micementioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

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confidence: 99%

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Adipocyte‐specific CDK7 ablation leads to progressive loss of adipose tissue and metabolic dysfunction

et al. 2022

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“…Specifically, p27 inhibits complexes of CDK2 and cyclin A (ccna) or E (ccne) and has a critical function in the negative regulation of cellular growth [ 24 ]. Apart from their functions in cell cycle regulation, several studies have revealed that some CDKs may play an important role in metabolism [ 21 ] such as CDK4, CDK5 or CDK7 [ 25 , 26 , 27 , 28 ]. Furthermore, adipose tissue-related functions have also been attributed to some cell cycle regulators.…”

Section: Introductionmentioning

confidence: 99%

Regulation of p27 and Cdk2 Expression in Different Adipose Tissue Depots in Aging and Obesity

Colón-Mesa

Fernández‐Galilea

Sáinz

et al. 2021

IJMS

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Aging usually comes associated with increased visceral fat accumulation, reaching even an obesity state, and favoring its associated comorbidities. One of the processes involved in aging is cellular senescence, which is highly dependent on the activity of the regulators of the cell cycle. The aim of this study was to analyze the changes in the expression of p27 and cdk2 in different adipose tissue depots during aging, as well as their regulation by obesity in mice. Changes in the expression of p27 and CDK2 in visceral and subcutaneous white adipose tissue (WAT) biopsies were also analyzed in a human cohort of obesity and type 2 diabetes. p27, but not cdk2, exhibits a lower expression in subcutaneous than in visceral WAT in mice and humans. p27 is drastically downregulated by aging in subcutaneous WAT (scWAT), but not in gonadal WAT, of female mice. Obesity upregulates p27 and cdk2 expression in scWAT, but not in other fat depots of aged mice. In humans, a significant upregulation of p27 was observed in visceral WAT of subjects with obesity. Taken together, these results show a differential adipose depot-dependent regulation of p27 and cdk2 in aging and obesity, suggesting that p27 and cdk2 could contribute to the adipose-tissue depot’s metabolic differences. Further studies are necessary to fully corroborate this hypothesis.

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The futile creatine cycle and the synthesis of fatty acids in inguinal white adipose tissue from growing rats, submitted to a hypoprotein‐hyperglycidic diet for 15 days

Allebrandt Neto,

Rondon e Silva,

Santos

et al. 2024

Lipids

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The low‐protein, high‐carbohydrate (LPHC) diet administered to growing rats soon after weaning, for 15 days, promoted an increase in energy expenditure by uncoupling protein 1 (UCP1) in interscapular brown adipose tissue, and also due to the occurrence of the browning process in the perirenal white adipose tissue (periWAT). However, we believe that inguinal white adipose tissue (ingWAT) may also contribute to energy expenditure through other mechanisms. Therefore, the aim of this work is to investigate the presence of the futile creatine cycle, and the origin of lipids in ingWAT, since that tissue showed an increase in the lipids content in rats submitted to the LPHC diet for 15 days. We observed increases in creatine kinase and alkaline phosphatase activity in ingWAT, of the LPHC animals. The mitochondrial Nicotinamide adenine dinucleotide reduced/nicotinamide adenine dinucleotide oxidized ratio is lower in ingWAT of LPHC animals. In the LPHC animals treated with β‐guanidinopropionic acid, the extracellular uptake of creatine in ingWAT was lower, as was the rectal temperature. Regarding lipid metabolism, we observed that in ingWAT, lipolysis in vitro when stimulated with noradrenaline is lower, and there were no changes in baseline levels. In addition, increases in the activity of enzymes were also observed: malic, glucose‐6‐phosphate dehydrogenase, and ATP‐citrate lyase, in addition to an increase in the PPARγ content. The results show the occurrence of the futile creatine cycle in ingWAT, and that the increase in the relative mass may be due to an increase in de novo fatty acid synthesis.

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CDK7 Mediates the Beta-Adrenergic Signaling in Thermogenic Brown and White Adipose Tissues

Cited by 11 publications

References 42 publications

Adipocyte‐specific CDK7 ablation leads to progressive loss of adipose tissue and metabolic dysfunction

Adipocyte‐specific CDK7 ablation leads to progressive loss of adipose tissue and metabolic dysfunction

Regulation of p27 and Cdk2 Expression in Different Adipose Tissue Depots in Aging and Obesity

The futile creatine cycle and the synthesis of fatty acids in inguinal white adipose tissue from growing rats, submitted to a hypoprotein‐hyperglycidic diet for 15 days

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