Chromosome 19 open reading frame 80 is upregulated by thyroid hormone and modulates autophagy and lipid metabolism

Tseng, Yi-Chuan; Ke, Po‐Yuan; Liao, Chien Wei; Wu, Sheng; Cheng, Hsiang; Tsai, Chun‐Yi; Chen, Cheng-Yi; Lin, Yan‐Hui; Lin, Kwang Huei

doi:10.4161/auto.26126

Cited by 74 publications

(88 citation statements)

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“…Consistent with the previous studies concluding that betatrophin might regulate lipid metabolism, possibly involving lipoprotein lipase activity (8,9,10,29,30), this study presented close associations of betatrophin with serum TC, HDL-C, and LDL-C rather than TG and low-density lipoprotein cholesterol (VLDL-C).…”

Section: Discussionsupporting

confidence: 78%

Aumento del nivel de betatrofina en suero en sujetos con síndrome metabólico: estudio de casos y controles

Zhu¹,

Li²,

Dai³

et al. 2016

Nutr Hosp

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ResumenIntroducción: la betatrofina es una novedosa adipoquina que provoca la proliferación de células β pancreáticas e interviene en el metabolismo de los lípidos. Objetivos: el propósito de este estudio es evaluar el papel de la betatrofina en el síndrome metabólico. Método: se llevó a cabo un estudio hospitalario de casos y controles según sexo y edad. El nivel de betatrofina en suero fue evaluado mediante ensayo por inmunoabsorción ligado a enzimas. Se midieron las concentraciones en suero de 12 adipoquinas para evaluar las asociaciones con la betatrofina usando los kits comerciales Adipokine Magnetic Bead Panel. Los análisis estadísticos incluyeron correlación bivariada, análisis de curva ROC y análisis de regresión lineal multivariable. Resultados: el nivel de betatrofina en suero fue más elevado en pacientes con síndrome metabólico (997,36 ± 475,92 pg/ml, p = 0,001) que en los controles (735,35 ± 526,51 pg/ml). Frente al tercil más bajo, el tercil más alto del nivel de betatrofina mostró una asociación con mayor riesgo de síndrome metabólico (odds ratio ajustado = 3,521, intervalo de confianza [IC] 95% [1,413], p = 0,023). Se desarrolló la curva ROC de betatrofina para pronosticar la presencia de síndrome metabólico (área bajo la curva ROC = 0,682 [95% IC, 0,597-0,767], p < 0,001). Además, la betatrofina mostró correlación con distintos parámetros, como edad (r = 0,286, p < 0,001), índice de masa corporal (r = 0,160, p = 0,046), índice cintura-cadera (r = 0,241, p = 0,002), lipoproteína de alta densidad (r = -0,167, p = 0,037), lipoproteína de baja densidad (r = -0,195, p = 0,015), glucosa plasmática en ayunas (r = 0,266, p = 0,001), hemoglobina A1C (r = 0,314, p < 0,001), índice de resistencia a la insulina mediante HOMA (r = 0,272, p = 0,001) y diversas adipoquinas, entre ellas resistina (r = 0,571, p < 0,001), interleucina-8 (r = 0,435, p < 0,001), factor de necrosis tumoral alfa (r = 0,295, p = 0,011) y lipocalina-2 (r = 0,346, p = 0,003). Conclusiones: este estudio demuestra que la betatrofina en suero desempeña una importante labor en el síndrome metabólico, implicando la regulación del metabolismo de la glucosa y los lípidos y la inflamación. AbstractBackground: Betatrophin is a novel adipokine that provokes pancreatic β-cell proliferation and is involved in lipid metabolism. Aims: This study aims to evaluate the role of serum betatrophin in metabolic syndrome (MetS). Methods: A hospital-based, age-/gender-matched case control study was conducted. The serum betatrophin level was evaluated by enzymelinked immunosorbent assay. Serum concentrations of 12 adipokines were measured to assess their associations with serum betatrophin, using commercial Adipokine Magnetic Bead Panel kits. Statistical analyses included bivariate correlation, receiver operating characteristic (ROC) curve, and multivariate stepwise linear regression. Conclusions: This study supports that serum betatrophin plays an important role in MetS, involving the regulations of glucose and lipid metabolism and inflammation.

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Section: Discussionsupporting

confidence: 78%

Aumento del nivel de betatrofina en suero en sujetos con síndrome metabólico: estudio de casos y controles

Zhu¹,

Li²,

Dai³

et al. 2016

Nutr Hosp

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“…20,27 We observed the co-occurrence of lipophagy and mitophagy at all the T 3 doses used in this study (1 to 100 nM) (Sinha and Yen, unpublished data); however, lipophagy was best visualized when cells were preloaded with exogenous fatty acids. Of note, we found that it was not necessary to preload cells with fatty acids to observe mitophagy, and since we used higher magnification images to visualize mitophagy events, endogenous lipid droplets in autophagosomes do not appear prominently in the EM images of this current study.…”

Section: Downloaded By [New York University] At 04:05 27 June 2015mentioning

confidence: 64%

“…Recently, we and others, 20,27 have shown that T 3 is a potent inducer of autophagy and this process is critical for β-oxidation of fatty acids and oxidative phosphorylation in mitochondria. However, it is not known whether T 3 -mediated autophagy participates in mitochondrial turnover.…”

Section: Downloaded By [New York University] At 04:05 27 June 2015mentioning

confidence: 99%

Thyroid hormone induction of mitochondrial activity is coupled to mitophagy via ROS-AMPK-ULK1 signaling

Sinha

Singh

Zhou³

et al. 2015

Autophagy

159

143

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Currently, there is limited understanding about hormonal regulation of mitochondrial turnover. Thyroid hormone (T3) increases oxidative phosphorylation (OXPHOS), which generates reactive oxygen species (ROS) that damage mitochondria. However, the mechanism for maintenance of mitochondrial activity and quality control by this hormone is not known. Here, we used both in vitro and in vivo hepatic cell models to demonstrate that induction of mitophagy by T3 is coupled to oxidative phosphorylation and ROS production. We show that T3 induction of ROS activates CAMKK2 (calcium/calmodulin-dependent protein kinase kinase 2, β) mediated phosphorylation of PRKAA1/AMPK (5' AMP-activated protein kinase), which in turn phosphorylates ULK1 (unc-51 like autophagy activating kinase 1) leading to its mitochondrial recruitment and initiation of mitophagy. Furthermore, loss of ULK1 in T3-treated cells impairs both mitophagy as well as OXPHOS without affecting T3 induced general autophagy/lipophagy. These findings demonstrate a novel ROS-AMPK-ULK1 mechanism that couples T3-induced mitochondrial turnover with activity, wherein mitophagy is necessary not only for removing damaged mitochondria but also for sustaining efficient OXPHOS.

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“…Moreover, Rab7 activation during nutrient stress also increases the association of Rab7-positive compartments with LDs [66]. Similarly, chromosome 19 open reading frame 80 (C19orf80) associates with LDs during thyroid hormone stimulation and mediates lipophagy in human hepatoma cell lines [67].…”

Section: Ld-vacuole/lysosome Interactionsmentioning

confidence: 99%

Lipid droplet–organelle interactions: emerging roles in lipid metabolism

Barbosa

Savage

Siniossoglou

2015

Current Opinion in Cell Biology

146

106

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Cellular homeostasis depends on the precisely coordinated use of lipids as fuels for energy production, building blocks for membrane biogenesis or chemical signals for intra-cellular and inter-cellular communication. Lipid droplets (LDs) are universally conserved dynamic organelles that can store and mobilize fatty acids and other lipid species for their multiple cellular roles. Increasing evidence suggests that contact zones between LDs and other organelles play important roles in the trafficking of lipids and in the regulation of lipid metabolism. Here we review recent advances regarding the nature and functional relevance of interactions between LDs and other organelles-particularly the endoplasmic reticulum (ER), LDs, mitochondria and vacuoles-that highlight their importance for lipid metabolism.

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Chromosome 19 open reading frame 80 is upregulated by thyroid hormone and modulates autophagy and lipid metabolism

Cited by 74 publications

References 50 publications

Aumento del nivel de betatrofina en suero en sujetos con síndrome metabólico: estudio de casos y controles

Aumento del nivel de betatrofina en suero en sujetos con síndrome metabólico: estudio de casos y controles

Thyroid hormone induction of mitochondrial activity is coupled to mitophagy via ROS-AMPK-ULK1 signaling

Lipid droplet–organelle interactions: emerging roles in lipid metabolism

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