PMID- 33368221
OWN - NLM
STAT- MEDLINE
DCOM- 20211007
LR  - 20211007
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 236
IP  - 7
DP  - 2021 Jul
TI  - Obesity-related genes are expressed in human Sertoli cells and modulated by 
      energy homeostasis regulating hormones.
PG  - 5265-5277
LID - 10.1002/jcp.30230 [doi]
AB  - The strong hormonal dysregulation associated with obesity is responsible for the 
      disruption of several reproductive events. Sertoli cells (SCs) function is 
      dependent on energetic homeostasis and thus, directly associated with energy 
      homeostasis regulating hormones. To further understand the influence of those 
      hormones with SCs function and obesity, we hypothesize that human SCs express 
      obesity-related genes (ORG; MC4R, GNPDA2, TMEM18, and FTO) and that they respond 
      to energy homeostasis regulating hormones (leptin, ghrelin, and glucagon-like 
      protein 1 [GLP-1]) stimuli. To test our hypothesis, SCs were cultured with 
      increasing doses of leptin (0, 5, 25, or 50 ng/ml, for 24 h), ghrelin (0, 20, 
      100, and 500 pM, for 24 h), and GLP-1 (10, 1000, or 1 x 105 pM, for 6 h). The 
      presence and abundance of ORG transcripts and proteins in SCs were accessed by 
      polymerase chain reaction techniques, Western blot analysis, and 
      immunofluorescence staining. Our results show that human SCs express MC4R, 
      GNPDA2, TMEM18, and FTO in specific cellular locations. MC4R and FTO expression 
      in human SCs was not responsive to the treatments. However, GNPDA2 and TMEM18 
      expression increased after exposure to the highest concentration of leptin and 
      ghrelin, respectively. We highlight for the first time that human SCs express ORG 
      and that these are responsive to energy homeostasis hormonal stimuli. GNPDA2 and 
      TMEM18 expression respond in opposite directions according to overall energy 
      status, mediated by energy homeostasis regulating hormones. Leptin and ghrelin 
      control of ORG expression by human SCs can be associated with overweight-related 
      infertility and subfertility in males.
CI  - (c) 2020 Wiley Periodicals LLC.
FAU - Pereira, Sara C
AU  - Pereira SC
AUID- ORCID: 0000-0003-2363-5431
AD  - Department of Microscopy, Laboratory of Cell Biology, and Unit for 
      Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel 
      Salazar, University of Porto, Porto, Portugal.
FAU - Martins, Ana C
AU  - Martins AC
AUID- ORCID: 0000-0002-7261-9596
AD  - Department of Microscopy, Laboratory of Cell Biology, and Unit for 
      Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel 
      Salazar, University of Porto, Porto, Portugal.
FAU - Moreira, Bruno P
AU  - Moreira BP
AUID- ORCID: 0000-0002-8584-4979
AD  - Department of Microscopy, Laboratory of Cell Biology, and Unit for 
      Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel 
      Salazar, University of Porto, Porto, Portugal.
FAU - Bernardino, Raquel L
AU  - Bernardino RL
AUID- ORCID: 0000-0002-1941-6634
AD  - Department of Microscopy, Laboratory of Cell Biology, and Unit for 
      Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel 
      Salazar, University of Porto, Porto, Portugal.
FAU - Barros, Alberto
AU  - Barros A
AUID- ORCID: 0000-0002-8700-3698
AD  - Department of Genetics, Faculty of Medicine, University of Porto, Porto, 
      Portugal.
AD  - i3S, Instituto de Investigacao e Inovacao em Saude, University of Porto, Porto, 
      Portugal.
AD  - Centre for Reproductive Genetics Professor Alberto Barros, Porto, Portugal.
FAU - Monteiro, Mariana P
AU  - Monteiro MP
AUID- ORCID: 0000-0002-0662-1831
AD  - Department of Anatomy and Unit for Multidisciplinary Research in Biomedicine, 
      Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, 
      Portugal.
FAU - Oliveira, Pedro F
AU  - Oliveira PF
AUID- ORCID: 0000-0002-4989-5699
AD  - QOPNA & LAQV, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
FAU - Alves, Marco G
AU  - Alves MG
AUID- ORCID: 0000-0001-7635-783X
AD  - Department of Microscopy, Laboratory of Cell Biology, and Unit for 
      Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel 
      Salazar, University of Porto, Porto, Portugal.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201223
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Ghrelin)
RN  - 0 (Leptin)
RN  - 0 (MC4R protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptor, Melanocortin, Type 4)
RN  - 0 (TMEM18 protein, human)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - EC 1.14.11.33 (Alpha-Ketoglutarate-Dependent Dioxygenase FTO)
RN  - EC 1.14.11.33 (FTO protein, human)
SB  - IM
MH  - Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism
MH  - Energy Metabolism/drug effects/*physiology
MH  - Ghrelin/pharmacology
MH  - Glucagon-Like Peptide 1/pharmacology
MH  - Homeostasis/*physiology
MH  - Humans
MH  - Leptin/pharmacology
MH  - Male
MH  - Membrane Proteins/metabolism
MH  - Obesity/*metabolism
MH  - Receptor, Melanocortin, Type 4/metabolism
MH  - Sertoli Cells/*metabolism
OTO - NOTNLM
OT  - GLP-1
OT  - Sertoli cells
OT  - ghrelin
OT  - leptin
OT  - obesity-related genes
OT  - spermatogenesis
EDAT- 2020/12/29 06:00
MHDA- 2021/10/08 06:00
CRDT- 2020/12/28 12:24
PHST- 2020/12/04 00:00 [revised]
PHST- 2020/09/17 00:00 [received]
PHST- 2020/12/08 00:00 [accepted]
PHST- 2020/12/29 06:00 [pubmed]
PHST- 2021/10/08 06:00 [medline]
PHST- 2020/12/28 12:24 [entrez]
AID - 10.1002/jcp.30230 [doi]
PST - ppublish
SO  - J Cell Physiol. 2021 Jul;236(7):5265-5277. doi: 10.1002/jcp.30230. Epub 2020 Dec 
      23.