Biological Effects of Ciliary Neurotrophic Factor on hMADS Adipocytes

Frontiers in Endocrinology

Saverio Cinti¹  Marco Tomasetti²  Federica Monaco²  Eleonora Di Mercurio³  Giovanni Tossetta³  Ilenia Severi³  Jessica Perugini³  Antonio Giordano³  Marcella Reguzzoni⁴  Christian Dani⁵ 

[1] Center of Obesity, United Hospitals, Marche Polytechnic University, Ancona, Italy;Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy;Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy;Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy;Université Côte d'Azur, CNRS, INSERM, iBV, Faculté de Médecine, Nice, France;

关键词: ciliary neurotrophic factor;    adipocytes;    JAK STAT pathway;    lipolysis;    mitochondria;    inflammation;   

DOI  :  10.3389/fendo.2019.00768

来源: DOAJ

【 摘 要 】

Administration of ciliary neurotrophic factor (CNTF) to experimental animals exerts anti-obesity effects by acting on multiple targets. In white adipose tissue CNTF reduces lipid content, promotes fatty acid (FA) oxidation and improves insulin sensitivity. This study was performed to establish whether CNTF exerts similar effects on human white adipocytes. To this end, adipose differentiation was induced in vitro in human multipotent adipose-derived stem (hMADS) cells. CNTF receptor α (CNTFRα) expression was assessed in hMADS cells and adipocytes by qRT-PCR, Western blotting, and immunocytochemistry. After administration of human recombinant CNTF, signaling pathways and gene expression were evaluated by Western blotting and qRT-PCR. Glucose uptake was assessed by measuring 2-nitrobenzodeoxyglucose uptake with a fluorescence plate reader. Lastly, CNTF-induced anti-inflammatory responses were evaluated in hMADS adipocytes stressed with tumor necrosis factor α (TNFα) for 24 h. Results showed that CNTFRα protein expression was higher in undifferentiated hMADS cells than in hMADS adipocytes, where it was however clearly detectable. In hMADS adipocytes, 1 nM CNTF strongly activated the JAK-STAT3 (Janus kinase-signaling transducer and activator of transcription 3) pathway and acutely and transiently activated the AMPK (AMP-activated protein kinase) and AKT (protein kinase B) pathways. Acute CNTF treatment for 20 min significantly increased basal glucose uptake and was associated with increased AKT phosphorylation. Longer-term (24 and 48 h) treatment reduced the expression of lipogenic markers (FA synthase and sterol regulatory element-binding protein-1) and increased the expression of lipolytic [hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL)] and mitochondrial (peroxisome proliferator-activated receptor γ coactivator-1α and carnitine palmitoyltransferase 1) markers. In TNFα-treated hMADS adipocytes, CNTF significantly reduced the expression of monocyte chemoattractant protein 1 and TNFα-induced AKT inhibition. Collectively, these findings demonstrate for the first time that CNTF plays a role also in human adipocytes, driving their metabolism toward a less lipid-storing and more energy-consuming phenotype.

【 授权许可】

Unknown