The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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Differing leukocyte gene expression profiles associated with fatigue

Discussion in 'Latest ME/CFS Research' started by Ecoclimber, Sep 26, 2013.

  1. Ecoclimber

    Ecoclimber Senior Member

    Differing leukocyte gene expression profiles associated with fatigue in patients with prostate cancer versus chronic fatigue syndrome.

    Light KC, Agarwal N, Iacob E, White AT, Kinney AY, Vanhaitsma TA, Aizad H, Hughen RW, Bateman L, Light AR.

    Department of Anesthesiology, University of Utah Health Sciences Center, Salt Lake City, UT, USA. Electronic address:


    Androgen deprivation therapy (ADT) often worsens fatigue in patients with prostate cancer, producing symptoms similar to chronic fatigue syndrome (CFS). Comparing expression (mRNA) of many fatigue-related genes in patients with ADT-treated prostate cancer versus with CFS versus healthy controls, and correlating mRNA with fatigue severity may clarify the differing pathways underlying fatigue in these conditions.

    Quantitative real-time PCR was performed on leukocytes from 30 fatigued, ADT-treated prostate cancer patients (PCF), 39 patients with CFS and 22 controls aged 40-79, together with ratings of fatigue and pain severity. 46 genes from these pathways were included: (1) adrenergic/monoamine/neuropeptides, (2) immune, (3) metabolite-detecting, (4) mitochondrial/energy, (5) transcription factors.

    PCF patients showed higher expression than controls or CFS of 2 immune transcription genes (NR3C1 and TLR4), chemokine CXCR4, and mitochondrial gene SOD2. They showed lower expression of 2 vasodilation-related genes (ADRB2 and VIPR2), 2 cytokines (TNF and LTA), and 2 metabolite-detecting receptors (ASIC3 and P2RX7). CFS patients showed higher P2RX7 and lower HSPA2 versus controls and PCF. Correlations with fatigue severity were similar in PCF and CFS for only DBI, the GABA-A receptor modulator (r=-0.50, p<0.005 and r=-0.34, p<0.05). Purinergic P2RY1 was correlated only with PCF fatigue and pain severity (r=+0.43 and +0.59, p=0.025 and p=0.001).

    PCF patients differed from controls and CFS in mean expression of 10 genes from all 5 pathways. Correlations with fatigue severity implicated DBI for both patient groups and P2RY1 for PCF only. These pathways may provide new targets for interventions to reduce fatigue.

    This a study that includes Dr. Bateman and the Lights

    More can be read here:

  2. Snow Leopard

    Snow Leopard Hibernating

    South Australia
    I haven't seen a discussion about this yet, so... (additonal note, threads have now been merged)
    Most of key details are listed there in the abstract.
    Side note, 43% of the post-cancer-fatigue controls had depression, with 51% of CFS patients and 0% of controls.

    I was interested in the association of reduced (relative) levels of DBI expression being correlated with increased fatigue.

    The finding may be nothing as a Japanese study found increased DBI expression in patients vs health controls.

    Now the role of DBI is interesting.

    DBI (diazepam binding inhibitor) is also known as the acyl-CoA-binding protein (ACBP) and plays a key role in regulating other systems including mitochondrial function.
    More functions are discussed in this paper:
    "Fatty acid transport and fatty acid-binding proteins"

    "Fat to the fire: the regulation of lipid oxidation with exercise and environmental stress"


    "Carnitine, mitochondrial function and therapy"
    "Fatty acyl-CoA–acyl-CoA-binding protein complexes activate the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum"

    But I wondered what effects mood, stress and exercise may have on expression.
    So I decided to dig a little deeper:
    "Acyl-coenzyme A binding protein expression is fibre-type specific in rat skeletal muscle but not affected by moderate endurance training"

    "Psychological stress, but not physical stress, causes increase in diazepam binding inhibitor (DBI) mRNA expression in mouse brains."
    And the DBI was subsequently reduced after administration of an agonist for central benzodiazepine receptors (Flunitrazepam).

    Perhaps more to be added soon...
    Valentijn, Sean, Firestormm and 2 others like this.
  3. LisaGoddard

    LisaGoddard Senior Member

    Thanks for these posts. I was intrigued that DBI affects so many systems - adrenal, insulin etc- that are out of whack with many of us.

    How would you promote the levels of DBI? I had a quick search which seemed to suggest acute stress, nicotine or morphine addiction. Mmmm... don't fancy any of these. I wondered about taking Acyl CoA?

    Any suggestions?

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