PMID- 38493915
OWN - NLM
STAT- MEDLINE
DCOM- 20240402
LR  - 20240402
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 970
DP  - 2024 May 5
TI  - Semaglutide 6-months therapy of type 2 diabetes mellitus restores adipose 
      progenitors potential to develop metabolically active adipocytes.
PG  - 176476
LID - S0014-2999(24)00164-X [pii]
LID - 10.1016/j.ejphar.2024.176476 [doi]
AB  - BACKGROUND: Nowadays type 2 diabetes mellitus (T2DM) leads to population 
      mortality growth. Today glucagon-like peptide type 1 receptor agonists (GLP-1 RA) 
      are one of the most promising glucose-lowered drugs with anorexigenic and 
      cardioprotective effects. The present study aims to determine the effects of 
      GLP-1 RA semaglutide 6-month therapy on T2DM patient metabolic parameters and 
      adipose progenitor cell health. METHODS: T2DM patients (N = 8) underwent clinical 
      characterization and subcutaneous fat biopsy at start point and after semaglutide 
      6-month therapy. Adipose-derived stem cells (ADSC) were isolated by enzymatic 
      method. Cell proliferation analysis was performed by MTT and immunocytochemistry. 
      White and beige adipogenesis was analyzed by BODIPY493/503 staining and confocal 
      microscopy. Adipocyte's metabolic properties were estimated by (3)H- and 
      (14)C-based metabolic assays. Thermogenesis analysis was performed by ERthermAC 
      staining and confocal microscopy. Protein markers were assessed by Western 
      blotting. RESULTS: Semaglutide 6-month therapy demonstrated significant 
      anorexigenic and glucose-lowering effects. However, insulin sensitivity (HOMA-IR 
      and M-index) was unchanged after therapy. Semaglutide 6-month therapy increased 
      ADSC proliferation and white and beige adipogenesis. Moreover, lipid droplets 
      fragmentation was observed in beige adipocytes. Both white and beige adipocytes 
      after semaglutide therapy demonstrated 2-3 fold growth of glucose uptake without 
      changes in insulin sensitivity. Newly formed white adipocytes demonstrated 
      glucose utilization for active ATP synthesis, whereas beige adipocytes for 
      canonical thermogenesis. CONCLUSIONS: Our study has revealed that semaglutide 
      6-month therapy has not only systemic anorexigenic effects, but can markedly 
      improve adipose tissue health. We have demonstrated critical restoration of ADSC 
      renewal functions, which potentially can be involved in semaglutide based weight 
      loss.
CI  - Copyright (c) 2024 Elsevier B.V. All rights reserved.
FAU - Stafeev, I
AU  - Stafeev I
AD  - National Medical Research Centre of Cardiology Named After Academician 
      E.I.Chazov, 121552, Moscow, Russia. Electronic address: yuristafeev@gmail.com.
FAU - Agareva, M
AU  - Agareva M
AD  - National Medical Research Centre of Cardiology Named After Academician 
      E.I.Chazov, 121552, Moscow, Russia; Lomonosov Moscow State University, 119991, 
      Moscow, Russia.
FAU - Michurina, S
AU  - Michurina S
AD  - National Medical Research Centre of Cardiology Named After Academician 
      E.I.Chazov, 121552, Moscow, Russia; Lomonosov Moscow State University, 119991, 
      Moscow, Russia.
FAU - Tomilova, A
AU  - Tomilova A
AD  - Endocrinology Research Centre, 117292, Moscow, Russia.
FAU - Shestakova, E
AU  - Shestakova E
AD  - Endocrinology Research Centre, 117292, Moscow, Russia.
FAU - Zubkova, E
AU  - Zubkova E
AD  - National Medical Research Centre of Cardiology Named After Academician 
      E.I.Chazov, 121552, Moscow, Russia.
FAU - Sineokaya, M
AU  - Sineokaya M
AD  - Endocrinology Research Centre, 117292, Moscow, Russia.
FAU - Ratner, E
AU  - Ratner E
AD  - National Medical Research Centre of Cardiology Named After Academician 
      E.I.Chazov, 121552, Moscow, Russia.
FAU - Menshikov, M
AU  - Menshikov M
AD  - National Medical Research Centre of Cardiology Named After Academician 
      E.I.Chazov, 121552, Moscow, Russia.
FAU - Parfyonova, Ye
AU  - Parfyonova Y
AD  - National Medical Research Centre of Cardiology Named After Academician 
      E.I.Chazov, 121552, Moscow, Russia; Lomonosov Moscow State University, 119991, 
      Moscow, Russia.
FAU - Shestakova, M
AU  - Shestakova M
AD  - Lomonosov Moscow State University, 119991, Moscow, Russia; Endocrinology Research 
      Centre, 117292, Moscow, Russia.
LA  - eng
PT  - Journal Article
DEP - 20240315
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 53AXN4NNHX (semaglutide)
RN  - IY9XDZ35W2 (Glucose)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 62340-29-8 (Glucagon-Like Peptides)
SB  - IM
MH  - Humans
MH  - Adipose Tissue, White/metabolism
MH  - *Diabetes Mellitus, Type 2/drug therapy/metabolism
MH  - Adipose Tissue, Brown/metabolism
MH  - *Insulin Resistance/physiology
MH  - Obesity/metabolism
MH  - Adipocytes, White/metabolism
MH  - Glucose/metabolism
MH  - Glucagon-Like Peptide 1/metabolism
MH  - *Glucagon-Like Peptides
OTO - NOTNLM
OT  - Adipocytes
OT  - Adipose-derived stem cells
OT  - GLP-1 analogues
OT  - Incretins
OT  - Obesity
OT  - Semaglutide
OT  - Type 2 diabetes
COIS- Declaration of competing interest The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: This study was supported by Russian Science Foundation grant 
      #22-15-00365.
EDAT- 2024/03/18 00:42
MHDA- 2024/04/02 06:46
CRDT- 2024/03/17 20:27
PHST- 2023/12/11 00:00 [received]
PHST- 2024/02/20 00:00 [revised]
PHST- 2024/03/01 00:00 [accepted]
PHST- 2024/04/02 06:46 [medline]
PHST- 2024/03/18 00:42 [pubmed]
PHST- 2024/03/17 20:27 [entrez]
AID - S0014-2999(24)00164-X [pii]
AID - 10.1016/j.ejphar.2024.176476 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2024 May 5;970:176476. doi: 10.1016/j.ejphar.2024.176476. Epub 
      2024 Mar 15.