bims-stacyt Biomed news
on Paracrine crosstalk between cancer and the organism
Issue of 2018‒06‒10
two papers selected by
Cristina Muñoz Pinedo
L’Institut d’Investigació Biomèdica de Bellvitge

  1. J Nutr Biochem. 2018 May 02. pii: S0955-2863(18)30043-3. [Epub ahead of print]58 17-27
    Lambertucci F, Arboatti A, Sedlmeier MG, Motiño O, Alvarez ML, Ceballos MP, Villar SR, Roggero E, Monti JA, Pisani G, Quiroga AD, Martín-Sanz P, Carnovale CE, Francés DE, Ronco MT.
      Obesity is accompanied by a low-grade inflammation state, characterized by increased proinflammatory cytokines levels such as tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL-1β). In this regard, there exists a lack of studies in hepatic tissue about the role of TNFα receptor 1 (TNFR1) in the context of obesity and insulin resistance during the progression of nonalcoholic fatty liver disease (NAFLD). The aim of this work was to evaluate the effects of high-caloric feeding (HFD) (40% fat, for 16 weeks) on liver inflammation-induced apoptosis, insulin resistance, hepatic lipid accumulation and its progression toward nonalcoholic steatohepatitis (NASH) in TNFR1 knock-out and wild-type mice. Mechanisms involved in HFD-derived IL-1β release and impairment of insulin signaling are still unknown, so we determined whether IL-1β affects liver insulin sensitivity and apoptosis through TNFα receptor 1 (TNFR1)-dependent pathways. We showed that knocking out TNFR1 induces an enhanced IL-1β plasmatic release upon HFD feed. This was correlated with higher hepatic and epididymal white adipose tissue mRNA levels. In vivo and in vitro assays confirmed an impairment in hepatic insulin signaling, in part due to IL-1β-induced decrease of AKT activation and diminution of IRS1 levels, followed by an increase in inflammation, macrophage (resident and recruited) accumulation, hepatocyte apoptotic process and finally hepatic damage. In addition, TNFR1 KO mice displayed higher levels of pro-fibrogenic markers. TNFR1 signaling disruption upon an HFD leads to an accelerated progression from simple steatosis to a more severe phenotype with many NASH features, pointing out a key role of TNFR1 in NAFLD progression.
    Keywords:  High-fat diet; IL-1 beta; IRS1; Inflammation; Insulin resistance; Nonalcoholic liver disease; TNFR1
  2. Eur J Intern Med. 2018 May 30. pii: S0953-6205(18)30229-2. [Epub ahead of print]
    Allegra A, Innao V, Gerace D, Allegra AG, Vaddinelli D, Bianco O, Musolino C.
      In addition to its capacity to store lipids the adipose tissue is now identified as a real organ with both endocrine and metabolic roles. Preclinical results indicate that modifying adipose tissue and bone marrow adipose tissue (BMAT) could be a successful multiple myeloma (MM) therapy. BMAT interrelates with bone marrow cells and other immune cells, and may influence MM disease progression. The BM adipocytes may have a role in MM progression, bone homing, chemoresistance, and relapse, due to local endocrine, paracrine, or metabolic factors. BM adipocytes isolated from MM subjects have been shown to increase myeloma growth in vitro and may preserve cells from chemotherapy-induced apoptosis. By producing free fatty acids and emitting signaling molecules such as growth factors and adipokines, BM adipocytes are both an energy font and an endocrine signaling factory. This review should suggest future research approaches toward developing novel treatments to target MM by targeting BMAT and its products.
    Keywords:  Adipocytes; Adipokine; Adipose tissue; Multiple myeloma; Myelomagenesis