bims-stacyt Biomed News
on Paracrine crosstalk between cancer and the organism
Issue of 2019‒10‒27
two papers selected by
Cristina Muñoz Pinedo
L’Institut d’Investigació Biomèdica de Bellvitge
  1. Differential metabolic and inflammatory responses to intermittent hypoxia in substrains of lean and obese C57BL/6 mice.
  2. Mitochondrial stress causes neuronal dysfunction via an ATF4-dependent increase in L-2-hydroxyglutarate.
  1. Life Sci. 2019 Oct 16. pii: S0024-3205(19)30886-0. [Epub ahead of print] 116959
    Differential metabolic and inflammatory responses to intermittent hypoxia in substrains of lean and obese C57BL/6 mice.
    Meng Qin Ge, Sze Chun Yeung, Judith Choi Wo Mak, Mary Sau Man Ip.
      AIMS: This study was to investigate the degree of susceptibility to intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), between the two mice inbred lines C57BL/6N (6N) and C57BL/6J (6J).MATERIALS AND METHODS: Four-week old male mice of 6N and 6J substrains (n = 8) were randomized to standard diet (SD) group or high fat (HF) diet group. At the age of 13-week, all two groups of mice were subjected to either air or IH (IH30; thirty hypoxic events per hour) for one week.
    KEY FINDINGS: All mice fed with HF diet exhibited obesity with more body weight and fat mass (percentage to body weight) gain. IH reduced serum LDL, HDL and total cholesterol levels in lean 6J mice. In obese mice, IH lowered obesity-induced serum total cholesterol level in 6J substrain but raised further in 6N substrain. Furthermore, IH caused elevation of serum FFA and MDA levels, and pro-inflammatory cytokines MCP-1 and IL-6 levels in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) of lean 6J but not lean 6N mice. There was reduced number of adipocytes and elevation of macrophages in SAT and VAT of HF-induced obese mice of both substrains. IH led to increased number of adipocytes and macrophages in SAT of lean 6J mice.
    SIGNIFICANCE: The genetic difference between 6N and 6J mice may have direct impact on metabolic and inflammatory responses after IH. Therefore, attention must be given for the selection of C57BL mice substrains in the experimental IH-exposed mouse model.
    Keywords:  Adipose tissue; Intermittent hypoxia (IH); Obesity; Obstructive sleep apnea (OSA); genetic background
    DOI:  https://doi.org/10.1016/j.lfs.2019.116959
  2. J Cell Biol. 2019 Oct 23. pii: jcb.201904148. [Epub ahead of print]
    Mitochondrial stress causes neuronal dysfunction via an ATF4-dependent increase in L-2-hydroxyglutarate.
    Rachel J Hunt, Lucy Granat, Gregory S McElroy, Ramya Ranganathan, Navdeep S Chandel, Joseph M Bateman.
      Mitochondrial stress contributes to a range of neurological diseases. Mitonuclear signaling pathways triggered by mitochondrial stress remodel cellular physiology and metabolism. How these signaling mechanisms contribute to neuronal dysfunction and disease is poorly understood. We find that mitochondrial stress in neurons activates the transcription factor ATF4 as part of the endoplasmic reticulum unfolded protein response (UPR) in Drosophila We show that ATF4 activation reprograms nuclear gene expression and contributes to neuronal dysfunction. Mitochondrial stress causes an ATF4-dependent increase in the level of the metabolite L-2-hydroxyglutarate (L-2-HG) in the Drosophila brain. Reducing L-2-HG levels directly, by overexpressing L-2-HG dehydrogenase, improves neurological function. Modulation of L-2-HG levels by mitochondrial stress signaling therefore regulates neuronal function.
    DOI:  https://doi.org/10.1083/jcb.201904148
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