bims-stacyt Biomed News
on Paracrine crosstalk between cancer and the organism
Issue of 2021‒04‒25
three papers selected by
Cristina Muñoz Pinedo
L’Institut d’Investigació Biomèdica de Bellvitge

  1. Front Endocrinol (Lausanne). 2021 ;12 653972
      In the past several decades obesity has become one of the greatest health burdens worldwide. Diet high in fats and fructose is one of the main causes for the prevalence of metabolic disorders including obesity. Promoting brown or beige adipocyte development and activity is regarded as a potential treatment of obesity. Mondo family transcription factors including MondoA and carbohydrate response element binding protein (ChREBP) are critical for nutrient-sensing in multiple metabolic organs including the skeletal muscle, liver, adipose tissue and pancreas. Under normal nutrient conditions, MondoA and ChREBP contribute to maintaining metabolic homeostasis. When nutrient is overloaded, Mondo family transcription factors directly regulate glucose and lipid metabolism in brown and beige adipocytes or modulate the crosstalk between metabolic organs. In this review, we aim to provide an overview of recent advances in the understanding of MondoA and ChREBP in sensing nutrients and regulating obesity or related pathological conditions.
    Keywords:  ChREBP; MondoA; brown and beige adipose tissue; nutrient-sensing; obesity
  2. JCI Insight. 2021 Apr 22. pii: 129429. [Epub ahead of print]6(8):
      It remains unresolved how retinal pigment epithelial cell metabolism is regulated following immune activation to maintain retinal homeostasis and retinal function. We exposed retinal pigment epithelium (RPE) to several stress signals, particularly Toll-like receptor stimulation, and uncovered an ability of RPE to adapt their metabolic preference on aerobic glycolysis or oxidative glucose metabolism in response to different immune stimuli. We have identified interleukin-33 (IL-33) as a key metabolic checkpoint that antagonizes the Warburg effect to ensure the functional stability of the RPE. The identification of IL-33 as a key regulator of mitochondrial metabolism suggests roles for the cytokine that go beyond its extracellular "alarmin" activities. IL-33 exerts control over mitochondrial respiration in RPE by facilitating oxidative pyruvate catabolism. We have also revealed that in the absence of IL-33, mitochondrial function declined and resultant bioenergetic switching was aligned with altered mitochondrial morphology. Our data not only shed new light on the molecular pathway of activation of mitochondrial respiration in RPE in response to immune stressors but also uncover a potentially novel role of nuclear intrinsic IL-33 as a metabolic checkpoint regulator.
    Keywords:  Glucose metabolism; Metabolism; Mitochondria; Ophthalmology; Retinopathy
  3. Inflamm Res. 2021 Apr 20.
      OBJECTIVE: To determine the involvement of TNF-α and glycine receptors in the inhibition of pro-inflammatory adipokines in 3T3-L1 cells.METHODS: RT-PCR evidenced glycine receptors in 3T3-L1 adipocytes. 3T3-L1 cells were transfected with siRNA for the glycine (Glrb) and TNF1a (Tnfrsf1a) receptors and confirmed by confocal microscopy. Transfected cells were treated with glycine (10 mM). The expressions of TNF-α and IL-6 mRNA were measured by qRT-PCR, while concentrations were quantified by ELISA.
    RESULTS: Glycine decreased the expression and concentration of TNF-α and IL-6; this effect did not occur in the absence of TNF-α receptor due to siRNA. In contrast, glycine produced only slight changes in the expression of TNF-α and IL-6 in the absence of the glycine receptor due to siRNA. A docking analysis confirmed the possibility of binding glycine to the TNF-α1a receptor.
    CONCLUSION: These findings support the idea that glycine could partially inhibit the binding of TNF-α to its receptor and provide clues about the mechanisms by which glycine inhibits the secretion of pro-inflammatory adipokines in adipocytes through the TNF-α receptor.
    Keywords:  Adipokines; Glycine receptor; Inflammation; TNF-α receptor; siRNA