Advances in Genetics of Regeneration in Metabesity

Gauthier, Benoit R.; Bermúdez‐Silva, Francisco Javier

doi:10.3390/genes10050383

Cited by 5 publications

(6 citation statements)

References 9 publications

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“…'Metabesity' is an emerging global term describing a wide range of diseases with underlying metabolic disorders and for which the etiology lies in complex interactions among genes and the obesogenic environment 1 . Metabesity contributes to the generation of a chronic low-grade inflammation 2 , which is recognized as the pathogenic link with Type 2 Diabetes Mellitus (T2DM).…”

Section: Introductionmentioning

confidence: 99%

The metabesity factor HMG20A potentiates astrocyte survival and reactive astrogliosis preserving neuronal integrity

Lorenzo¹,

Vázquez²,

López-Noriega³

et al. 2021

Theranostics

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Rationale: We recently demonstrated that the 'Metabesity' factor HMG20A regulates islet beta-cell functional maturity and adaptation to physiological stress such as pregnancy and pre-diabetes. HMG20A also dictates central nervous system (CNS) development via inhibition of the LSD1-CoREST complex but its expression pattern and function in adult brain remains unknown. Herein we sought to determine whether HMG20A is expressed in the adult CNS, specifically in hypothalamic astrocytes that are key in glucose homeostasis and whether similar to islets, HMG20A potentiates astrocyte function in response to environmental cues. Methods: HMG20A expression profile was assessed by quantitative PCR (QT-PCR), Western blotting and/or immunofluorescence in: 1) the hypothalamus of mice exposed or not to either a high-fat diet or a high-fat high-sucrose regimen, 2) human blood leukocytes and adipose tissue obtained from healthy or diabetic individuals and 3) primary mouse hypothalamic astrocytes exposed to either high glucose or palmitate. RNA-seq and cell metabolic parameters were performed on astrocytes treated or not with a siHMG20A. Astrocyte-mediated neuronal survival was evaluated using conditioned media from siHMG20A-treated astrocytes. The impact of ORY1001, an inhibitor of the LSD1-CoREST complex, on HMG20A expression, reactive astrogliosis and glucose metabolism was evaluated in vitro and in vivo in high-fat high-sucrose fed mice. Results: We show that Hmg20a is predominantly expressed in hypothalamic astrocytes, the main nutrient-sensing cell type of the brain. HMG20A expression was upregulated in diet-induced obesity and glucose intolerant mice, correlating with increased transcript levels of Gfap and Il1b indicative of inflammation and reactive astrogliosis. Hmg20a transcript levels were also increased in adipose tissue of obese non-diabetic individuals as compared to obese diabetic patients. HMG20A silencing in astrocytes resulted in repression of inflammatory, cholesterol biogenesis and epithelial-to-mesenchymal transition pathways which are hallmarks of reactive astrogliosis. Accordingly, HMG20A depleted astrocytes exhibited reduced mitochondrial bioenergetics and increased susceptibility to apoptosis. Neuron viability was also hindered in HMG20A-depleted astrocyte-derived conditioned media. ORY1001 treatment rescued expression of reactive astrogliosis-linked genes in HMG20A ablated astrocytes while enhancing cell surface area, GFAP intensity and STAT3 expression in healthy astrocytes, mimicking the effect of HMG20A. Furthermore, ORY1001 treatment protected against obesity-associated glucose intolerance in mice correlating with a regression of hypothalamic HMG20A expression, indicative of reactive astrogliosis attenuation with improved health status. Conclusion: HMG20A coordinates the astrocy...

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Section: Introductionmentioning

confidence: 99%

The metabesity factor HMG20A potentiates astrocyte survival and reactive astrogliosis preserving neuronal integrity

Lorenzo¹,

Vázquez²,

López-Noriega³

et al. 2021

Theranostics

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“…Coubertin'e göre, "siyasi coğrafya" ile "sporun coğrafyası" birbirinden ayrılmalıdır 92 . İlerleyen süreç içerisinde bu anlayış devam etmiş olsa da, Uluslararası Olimpiyat Komitesi kuralları 1996 senesinde değişikliğe uğramıştır 93 . Değişiklik sonrasında, Milli Olimpiyat Komitesinin artık "uluslararası toplum tarafından tanınan bağımsız bir devleti" temsil etmesi beklenmiştir 94 .…”

Section: Kuzey Kıbrıs Türk Cumhuriyeti Vatandaşı Olan Sporcuların Durumuunclassified

“…Değişiklik sonrasında, Milli Olimpiyat Komitesinin artık "uluslararası toplum tarafından tanınan bağımsız bir devleti" temsil etmesi beklenmiştir 94 . Bu gelişmeye rağmen her ne kadar Birleşmiş Milletler tarafından devlet olarak tanınmasa da 2014 senesinde Kosova, Uluslararası Olimpiyat Komitesi tarafından tanınmıştır 95 . İlgili tanıma işleminin gerçekleşebilmesinde, diğer birçok Milli Olimpiyat Komitesi'nin ve Uluslararası Federasyon'un Kosova'yı tanımış olmasının rolü vardır 96 .…”

Section: Kuzey Kıbrıs Türk Cumhuriyeti Vatandaşı Olan Sporcuların Durumuunclassified

Participation of Athletes Who Are Citizens of the Turkish Republic of Northern Cyprus in International Competitions in Terms of International Law

CANDAN,

HALHALLI

2023

İnönü Üniversitesi Hukuk Fakültesi Dergisi

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Günümüzde spor faaliyetlerinin giderek endüstrileşmesi, spor alanının da küreselleşmesi sonucunu doğurmaktadır. Sportif müsabakaların uluslararası naklen yayınlanması, ulusal liglerde yer alan kulüplerin farklı ülkelerde taraftar gruplarına sahip olmasına yol açarken, yabancı uyruklu sporcuların vatandaşlık değiştirerek farklı ulusal takımlarda yer almaları da artık sıradan olaylar haline gelmiştir. Ulusal kupa finallerinin farklı ülkelerde oynanması da son dönemde sporseverleri şaşırtmamaktadır. Öte yandan, sporun küreselleşmesi olgusundan hala yararlanamayan ülke sporcularının varlığı da bir başka gerçeklik olarak karşımıza çıkmaktadır. Özellikle Kuzey Kıbrıs Türk Cumhuriyeti devletinin uluslararası toplum tarafından hala tanınmaması, KKTC vatandaşı olan sporcuların durumunu da doğrudan olumsuz etkilemektedir. Her ne kadar Birleşmiş Milletler Genel Kurulu tarafından 17 Kasım 2003 tarihinde kabul edilmiş 58/5 No’lu Karar ile sporun; eğitim, sağlık, kalkınma ve barışı teşvik etmek için önemli bir araç olarak kabul edilmesi gerektiği vurgulanmışsa da, söz konusu kararın, KKTC vatandaşı sporcuların uluslararası spor müsabakalarına katılmasına yönelik herhangi bir olumlu etkisi olmamıştır. Özellikle Uluslararası Olimpiyat Komitesi tarafından KKTC vatandaşı sporcuların ve spor takımlarının düzenlenen organizasyonlara katılımının engellenmesi konusu, spor hukuku açısından olduğu kadar uluslararası hukuk normları açısından da tartışılmalıdır. Bu makalede öncelikle spor hukukunun özel yapısı ve uluslararası örgütlenmesi genel hatlarıyla incelenecektir. Sonrasında ise uluslararası spor hukuku açısından KKTC vatandaşı sporcuların ve spor kulüplerinin uluslararası müsabakalara katılımı ele alınacaktır.

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“…‘Metabesity’ is an emerging global term describing a wide range of diseases with underlying metabolic disorders and for which the etiology lies in complex interactions among genes and the obesogenic environment [1, 2]. Metabesity contributes to the generation of a chronic low-grade inflammation [3], which is recognized as the pathogenic link with Type 2 Diabetes Mellitus (T2DM).…”

Section: Introductionmentioning

confidence: 99%

The Metabesity Factor HMG20A Potentiates Astrocyte Survival and Reactivity Preserving Neuronal Integrity

Lorenzo

Fuente-Martín

Mellado-Gil

et al. 2021

Preprint

Self Cite

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Rationale: We recently demonstrated that the Metabesity factor HMG20A regulates islet beta-cell functional maturity and adaptation to physiological stress such as pregnancy and pre-diabetes. HMG20A also dictates central nervous system (CNS) development via inhibition of the LSD1/CoREST complex but its expression pattern and function in the adult brain remains unknown. Herein we sought to determine whether HMG20A is expressed in the adult CNS, specifically in hypothalamic astrocytes that are key in glucose homeostasis and whether similar to islets, HMG20A potentiates astrocyte function in response to environmental cues. Methods: HMG20A expression profile was assessed by quantitative PCR (RT-PCR) and/or immunofluorescence in 1) the hypothalamus of mice exposed or not to a high-fat diet, 2) human blood leukocytes and adipose tissue obtained from healthy or diabetic individuals 3) primary mouse hypothalamic astrocytes exposed to either high glucose or palmitate. To investigate the function and regulatory mechanism of HMG20A, RNA-seq and cell metabolic parameters were performed on astrocytes treated or not with a siHMG20A. The regulatory function of HMG20A on astrogliosis was also assessed pharmacologically using ORY1001. Astrocyte-mediated neuronal survival was evaluated using conditioned media from siHMG20A-treated astrocytes. Results: We show that Hmg20a is predominantly expressed in hypothalamic astrocytes, the main nutrient-sensing cell type of the brain. Hmg20A expression was upregulated in diet-induced obesity and glucose-intolerant mice, correlating with increased transcript levels of Gfap and Il1b indicative of inflammation and astrogliosis. Expression levels were also increased in adipose tissue of obese non-diabetic individuals as compared to obese diabetic patients. HMG20A silencing in astrocytes resulted in repression of inflammatory, cholesterol biogenesis and epithelial-to-mesenchymal transition pathways with a concomitant increase in apoptosis and reduced mitochondrial bioenergetics. Motoneuron viability was also hindered in HMG20A-depleted astrocyte-derived conditioned media. Astrogliosis was induced using ORY1001, a pharmacological inhibitor of the LSD1/CoREST complex, mimicking the effect of HMG20A. Conclusion: HMG20A coordinates the astrocyte polarization state. Under physiological pressure such as obesity and insulin resistance that induces low-grade inflammation, HMG20A expression is increased to induce astrogliosis in an attempt to preserve the neuronal network and glucose homeostasis. Nonetheless, a chronic metabesity state or functional mutations will result in lower levels of HMG20A, failure to promote astrogliosis and increase the susceptibility of neurons to stress-mediated apoptosis. Such effects could be therapeutically reversed by ORY1001-induced astrogliosis.

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Advances in Genetics of Regeneration in Metabesity

Cited by 5 publications

References 9 publications

The metabesity factor HMG20A potentiates astrocyte survival and reactive astrogliosis preserving neuronal integrity

The metabesity factor HMG20A potentiates astrocyte survival and reactive astrogliosis preserving neuronal integrity

Participation of Athletes Who Are Citizens of the Turkish Republic of Northern Cyprus in International Competitions in Terms of International Law

The Metabesity Factor HMG20A Potentiates Astrocyte Survival and Reactivity Preserving Neuronal Integrity

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