Immunometabolism mRNA expression phenotypes and reprogramming of CD14 in T2DM with or without CVD.
CD14
Immunometabolic
Leptin
PPARγ
Phenotype
STAT1
STAT6
T2DM
Journal
International immunopharmacology
ISSN: 1878-1705
Titre abrégé: Int Immunopharmacol
Pays: Netherlands
ID NLM: 100965259
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
received:
06
02
2023
revised:
28
06
2023
accepted:
16
07
2023
medline:
25
8
2023
pubmed:
24
7
2023
entrez:
24
7
2023
Statut:
ppublish
Résumé
Type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) have a significant impact on the expression of genes in peripheral blood mononuclear cells (PBMCs). The primary objective of this study was to investigate the role of two signaling pathways, STAT1/6, and two important modulators of immunometabolism, leptin and PPARs, in the development of T2DM with and without CVD. Furthermore, the study aimed to assess the correlation between these factors and the dynamics of CD14 in PBMCs. This research was conducted within the context of a growing body of literature on the complex pathophysiology of T2DM and its association with CVD. Prior studies have indicated that T2DM is characterized by an imbalance in immunometabolism and the involvement of various signaling pathways. Blood samples were collected from a total of 47 subjects, including 7 healthy volunteers, 20 individuals diagnosed with diabetes and cardiovascular disease (D.CVD) and another 20 individuals diagnosed with diabetes only (D). PBMCs were isolated from these samples, and the expression levels of leptin, PPARγ, PPARα, and CD14 genes were measured using Real-Time PCR. The most relevant result showed that diabetic patients with CVD had significantly higher levels of leptin expression, which was positively correlated with STAT1 (r = 0.7497, p = 0.0001). On the other hand, diabetic patients without CVD had elevated PPARγ expression, which was strongly correlated with STAT6 (r = 0.8437, p = 0.0001). Interestingly, we found a significant increase in the PPARγ/ PPARα ratio in the D.CVD group compared to the D group (4.273 ± 0.9531; 7.52 ± 3.556, p = 0.0479). Moreover, CD14 expression was significantly reduced in this group compared to diabetic patients without CVD. These findings suggested that the immunometabolic imbalance in T2DM was driven by a STAT1/Leptin phenotype in diabetic patients with CVD and by a STAT6/PPARγ phenotype in diabetic patients without CVD. Taking into account STAT1/Leptin and STAT6/PPARγ profiling could help clinicians identify novel therapeutic targets for T2DM and other related diseases.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) have a significant impact on the expression of genes in peripheral blood mononuclear cells (PBMCs). The primary objective of this study was to investigate the role of two signaling pathways, STAT1/6, and two important modulators of immunometabolism, leptin and PPARs, in the development of T2DM with and without CVD. Furthermore, the study aimed to assess the correlation between these factors and the dynamics of CD14 in PBMCs. This research was conducted within the context of a growing body of literature on the complex pathophysiology of T2DM and its association with CVD. Prior studies have indicated that T2DM is characterized by an imbalance in immunometabolism and the involvement of various signaling pathways.
MATERIALS AND METHODS
METHODS
Blood samples were collected from a total of 47 subjects, including 7 healthy volunteers, 20 individuals diagnosed with diabetes and cardiovascular disease (D.CVD) and another 20 individuals diagnosed with diabetes only (D). PBMCs were isolated from these samples, and the expression levels of leptin, PPARγ, PPARα, and CD14 genes were measured using Real-Time PCR.
RESULTS
RESULTS
The most relevant result showed that diabetic patients with CVD had significantly higher levels of leptin expression, which was positively correlated with STAT1 (r = 0.7497, p = 0.0001). On the other hand, diabetic patients without CVD had elevated PPARγ expression, which was strongly correlated with STAT6 (r = 0.8437, p = 0.0001). Interestingly, we found a significant increase in the PPARγ/ PPARα ratio in the D.CVD group compared to the D group (4.273 ± 0.9531; 7.52 ± 3.556, p = 0.0479). Moreover, CD14 expression was significantly reduced in this group compared to diabetic patients without CVD.
CONCLUSION
CONCLUSIONS
These findings suggested that the immunometabolic imbalance in T2DM was driven by a STAT1/Leptin phenotype in diabetic patients with CVD and by a STAT6/PPARγ phenotype in diabetic patients without CVD. Taking into account STAT1/Leptin and STAT6/PPARγ profiling could help clinicians identify novel therapeutic targets for T2DM and other related diseases.
Identifiants
pubmed: 37487262
pii: S1567-5769(23)00990-6
doi: 10.1016/j.intimp.2023.110665
pii:
doi:
Substances chimiques
Leptin
0
PPAR gamma
0
PPAR alpha
0
RNA, Messenger
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
110665Informations de copyright
Copyright © 2023 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.