PMID- 29867095
OWN - NLM
STAT- MEDLINE
DCOM- 20191129
LR  - 20240326
IS  - 2041-4889 (Electronic)
VI  - 9
IP  - 6
DP  - 2018 Apr 22
TI  - Metabolic patterns in insulin-resistant male hypogonadism.
PG  - 671
LID - 10.1038/s41419-018-0587-9 [doi]
LID - 671
AB  - Male hypogonadism associated with insulin resistance (IR) very often leads to 
      metabolic syndrome, at variance with hypogonadism in its first stadium of insulin 
      sensitivity (IS). A plasma metabolomic investigation of these patients can 
      provide useful information in comparison with the values of IS patients. To this 
      aim plasma from insulin-resistant males with hypogonadism were analysed by using 
      ultra high-performance liquid chromatography (UHPLC) and high-resolution mass 
      spectrometry (HRMS). Thus, metabolites were compared to the controls through 
      multivariate statistical analysis and grouped by metabolic pathways. Metabolite 
      database searches and pathway analyses identified imbalances in 18-20 metabolic 
      pathways. Glucose metabolism (e.g., glycolysis and the Krebs cycle) is fuelled by 
      amino acids degradation, in particular of branched amino acids, in individuals 
      with lean body mass. Gluconeogenesis is strongly activated. Some crucial pathways 
      such as glycerol are skewed. Mitochondrial electron transport is affected with a 
      reduction in ATP production. Beta-oxidation of short and medium chain fatty acids 
      did not represent an energy source in hypogonadism, at variance with long and 
      branched fatty acids, justifying the increase in fat mass. Carnosine and 
      beta-alanine are strongly reduced resulting in increased fatigue and mental 
      confusion. A comparison of IR with IS male hypogonadism will contribute to a 
      better understanding of how these two hormones work in synergy or antagonise each 
      other in humans. It could also help to select patients who will respond to 
      hormone treatment, and provide accurate biomarkers to measure the response to 
      treatment eventually leading to better strategies in preventing systemic 
      complications in patients not fit for hormone replacement therapy.
FAU - Gevi, Federica
AU  - Gevi F
AD  - Department of Science and Technology for Agriculture, Forestry, Nature and Energy 
      (DAFNE), University of Tuscia, Viterbo, Italy.
FAU - Fanelli, Giuseppina
AU  - Fanelli G
AD  - Department of Ecological and Biological Sciences (DEB), University of Tuscia, 
      Viterbo, Italy.
FAU - Zolla, Lello
AU  - Zolla L
AD  - Department of Science and Technology for Agriculture, Forestry, Nature and Energy 
      (DAFNE), University of Tuscia, Viterbo, Italy. zolla@unitus.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180422
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Amino Acids)
RN  - 11P2JDE17B (beta-Alanine)
RN  - 72-89-9 (Acetyl Coenzyme A)
RN  - 8HO6PVN24W (Carnosine)
RN  - IY9XDZ35W2 (Glucose)
RN  - PDC6A3C0OX (Glycerol)
SB  - IM
MH  - Acetyl Coenzyme A/metabolism
MH  - Adult
MH  - Amino Acids/blood
MH  - Carnosine/metabolism
MH  - Citric Acid Cycle
MH  - Glucose/metabolism
MH  - Glycerol/metabolism
MH  - Glycolysis
MH  - Humans
MH  - Hypogonadism/blood/*metabolism
MH  - *Insulin Resistance
MH  - Male
MH  - Metabolome
MH  - Metabolomics
MH  - Middle Aged
MH  - beta-Alanine/metabolism
PMC - PMC5986816
COIS- The authors declare that they have no conflict of interest.
EDAT- 2018/06/06 06:00
MHDA- 2019/11/30 06:00
PMCR- 2018/04/22
CRDT- 2018/06/06 06:00
PHST- 2018/01/31 00:00 [received]
PHST- 2018/04/12 00:00 [accepted]
PHST- 2018/03/28 00:00 [revised]
PHST- 2018/06/06 06:00 [entrez]
PHST- 2018/06/06 06:00 [pubmed]
PHST- 2019/11/30 06:00 [medline]
PHST- 2018/04/22 00:00 [pmc-release]
AID - 10.1038/s41419-018-0587-9 [pii]
AID - 587 [pii]
AID - 10.1038/s41419-018-0587-9 [doi]
PST - epublish
SO  - Cell Death Dis. 2018 Apr 22;9(6):671. doi: 10.1038/s41419-018-0587-9.