DBC1 is involved in adipocyte inflammation and is a possible marker of human adipose tissue senescence

Moreno-Navarrete, José María; Moreno, María; Vidal, Marta; Ortega, Francisco; Ricart, Wifredo; Fernández-Real, José Manuel

doi:10.1002/oby.20999

Cited by 20 publications

(19 citation statements)

References 20 publications

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“…Of more clinical relevance, it has been shown that high-fat diet can reduce SIRT1 levels in white adipose by inflammatorymediated caspase 1 [144], and in turn, resveratrol supplementation in high-fat diet fed rhesus monkeys prevents adipose tissue inflammation [145]. Most recently, an inhibitor of SIRT1, deleted in breast cancer 1, was shown to be involved in regulating adipose tissue inflammation and adipose tissue senescence using deleted in breast cancer 1 knockout mice, and was shown to positively correlate with proinflammatory markers in both subcutaneous and visceral adipose tissue in morbidly obese [146]. Similarly, considerable research has shown that sirtuin function, most notably SIRT1 and SIRT6, is involved in regulating the inflammatory response in myeloid and lymphoid cells that can infiltrate the adipose tissue.…”

Section: Sirtuin Control Of Inflammationmentioning

confidence: 99%

The sirtuins: Markers of metabolic health

Covington

Bajpeyi

2015

Molecular Nutrition Food Res

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The sirtuins represent a class of proteins first discovered orthologus to the yeast silent information regulator 2 protein that have been retained in mammalian species. Currently, seven sirtuins have been identified in humans, and their functions currently surpass their originally identified role as histone deacetylase and chromatin silencers to encompass nutrient sensing and metabolic function. All seven sirtuins require NAD(+) in order to carry out their enzymatic activity, and thus become activated in conditions of nutrient depletion, starvation, and cellular stress. Caloric restriction and increased physical activity have been postulated, though perhaps controversially, to mediate sirtuin function. Here, we review the current literature surrounding the functions of the seven human sirtuins, mediators of their function, and the roles they play in metabolic health related to dietary and physical activity interventions. Despite the controversy surrounding sirtuin function with regard to longevity, we have aimed to show that regardless of its effects on aging, sirtuin function is pivotal to pathways involving metabolic health, and should therefore be investigated with regard to improving metabolic diseases such as obesity and type 2 diabetes.

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Section: Sirtuin Control Of Inflammationmentioning

confidence: 99%

The sirtuins: Markers of metabolic health

Covington

Bajpeyi

2015

Molecular Nutrition Food Res

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“…Increased TSH mRNA levels and circulating TSH were significantly associated with reduced markers of cellular senescence (including BAX, DBC1, TP53, TNF gene expression [12,13] and specific glucosylceramides [21,23]) and increased telomere length in both human and rat AT. These data agree with the positive association between serum TSH levels and longevity reported in rodents [1][2][3] and euthyroid humans [3][4][5][6][7][8][9].…”

Section: Discussionmentioning

confidence: 97%

“…Adipose tissue cellular senescence is characterized by increased expression of apoptotic and senescence markers (caspase induction leading to increased BAX, TP53 and DBC1 expression), decreased telomere length [11][12][13][14][15], and impaired capacity to generate new adipocytes and mitochondrial dysfunction [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Adipose TSHB in Humans and Serum TSH in Hypothyroid Rats Inform About Cellular Senescence

Moreno-Navarrete

Liñares-Pose

Sabater

et al. 2018

Cell Physiol Biochem

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Background/Aims: Thyroid hormones have been recently linked to senescence and longevity. Given the recent description of TSHB mRNA in human adipose tissue (AT), we aimed to investigate the relationship between local AT TSH and adipose tissue senescence. Methods: TSHB mRNA (measured by real-time PCR) and markers of adipose tissue senescence [BAX, DBC1, TP53, TNF (real-time PCR), telomere length (Telo TAGGG Telomere Length Assay) and lipidomics (liquid chromatography mass spectrometry)] were analysed in subcutaneous (SAT) and visceral (VAT) AT from euthyroid subjects. The chronic effects of TSH were also investigated in AT from hypothyroid rats and after recombinant human TSH (rhTSH) administration in human adipocytes. Results: Both VAT and SAT TSHB gene expression negatively correlated with markers of AT cellular senescence (BAX, DBC1, TP53, TNF gene expression and specific glucosylceramides) and positively associated with telomere length. Supporting these observations, both rhTSH administration in human adipocytes and increased TSH in hypothyroid rats resulted in decreased markers of cellular senescence (Bax and Tp53 mRNA) in both gonadal and subcutaneous white adipose tissue. Conclusion: These data point to a possible role of TSH in AT cellular senescence.

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“…We and others have extensively shown that DBC1 plays major roles in metabolism and metabolic diseases 19,22,[31][32][33][34][35] . DBC1 regulates SIRT1 activity in the liver and adipose tissue during different metabolic states 22,31 .…”

Section: Discussionmentioning

confidence: 99%

“…Many lines of research support that DBC1 is involved in the control of metabolism and metabolic diseases 19,22,[31][32][33][34] . We also showed that DBC1 KO mice have increased SIRT1 activity in vivo in liver and they are protected against non-alcoholic fatty liver disease 22 .…”

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confidence: 99%

The protein Deleted in Breast Cancer-1 (DBC1) regulates vascular response and formation of aortic dissection during Angiotensin II infusion

Colman

Caggiani

Leyva

et al. 2020

Sci Rep

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Cardiovascular diseases are among the main causes of morbimortality in the adult population. Among them, hypertension is a leading cause for stroke, heart disease and kidney failure. Also, as a result of arterial wall weakness, hypertension can lead to the development of dissecting aortic aneurysms, a rare but often fatal condition if not readily treated. In this work, we investigated the role of DBC1 in the regulation of vascular function in an ANGII-induced hypertension mouse model. We found that WT and DBC1 KO mice developed hypertension in response to ANGII infusion. However, DBC1 KO mice showed increased susceptibility to develop aortic dissections. The effect was accompanied by upregulation of vascular remodeling factors, including MMP9 and also VEGF. Consistent with this, we found decreased collagen deposition and elastic fiber fragmentation, suggesting that increased expression of MMPs in DBC1 KO mice weakens the arterial wall, promoting the formation of aortic dissections during treatment with ANGII. Finally, DBC1 KO mice had reduced cell proliferation in the intima-media layer in response to ANGII, paralleled with an impairment to increase wall thickness in response to hypertension. Furthermore, VSMC purified from DBC1 KO mice showed impaired capacity to leave quiescence, confirming the in vivo results. Altogether, our results show for the first time that DBC1 regulates vascular response and function during hypertension and protects against vascular injury. This work also brings novel insights into the molecular mechanisms of the development of aortic dissections.General reagents and antibodies. All general reagents and chemicals were purchased from Sigma-Aldrich, including angiotensin II (ANGII, A9525), unless otherwise specified. Lipofectamine RNAiMax, Bradford protein assay reagent, Trizol and SuperScript II RT were bought from Invitrogen. SiRNAs oligos were purchased from Ambion (Negative Control 4390843; HDAC3 4390771) or Invitrogen (DBC1 MSS211964 and SIRT1 MSS234959). Antibodies were purchased from Bethyl (anti DBC1, 434 A), Abcam (anti tubulin 7291, anti BrdU 6326, anti KI67 16667), or Cell Signaling (anti Cyclin D1 9262, anti PCNA 92552). DNase I and Fast SYBR Green were purchased from Roche.Animal handling and experiments. All mice used in this study were maintained at the Institut Pasteur de Montevideo Animal facility (UATE). The experimental protocol was approved by the Institutional Animal Care and Use Committee of the Institut Pasteur de Montevideo (CEUA, Protocol number 014-14). All the studies described were performed according to the methods approved in the protocol and following all international guidelines and legal regulations. WT and whole-body DBC1 KO mice were in a C57BL6/J pure background. DBC1 KO mice were backcrossed into C57BL/6 J for more than 10 generations in order to ensure genetic purity. Mice received standard chow and water ad libitum. Scientific RepoRtS |(2020) 10:6772 | https://doi.negative control, DBC1, HDAC3 and SIRT1 using 25 pmol Lipofectamine RNAiMax. After 24 h...

show abstract

DBC1 is involved in adipocyte inflammation and is a possible marker of human adipose tissue senescence

Cited by 20 publications

References 20 publications

The sirtuins: Markers of metabolic health

The sirtuins: Markers of metabolic health

Adipose TSHB in Humans and Serum TSH in Hypothyroid Rats Inform About Cellular Senescence

The protein Deleted in Breast Cancer-1 (DBC1) regulates vascular response and formation of aortic dissection during Angiotensin II infusion

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