TY  - JOUR
A1  - Hauffe, Robert
A1  - Rath, Michaela
A1  - Agyapong, Wilson
A1  - Jonas, Wenke
A1  - Vogel, Heike
A1  - Schulz, Tim Julius
A1  - Schwarz, Maria
A1  - Kipp, Anna Patricia
A1  - Blüher, Matthias
A1  - Kleinridders, André
T1  - Obesity Hinders the Protective Effect of Selenite Supplementation on Insulin Signaling
JF  - Antioxidants
N2  - The intake of high-fat diets (HFDs) containing large amounts of saturated long-chain fatty acids leads to obesity, oxidative stress, inflammation, and insulin resistance. The trace element selenium, as a crucial part of antioxidative selenoproteins, can protect against the development of diet-induced insulin resistance in white adipose tissue (WAT) by increasing glutathione peroxidase 3 (GPx3) and insulin receptor (IR) expression. Whether selenite (Se) can attenuate insulin resistance in established lipotoxic and obese conditions is unclear. We confirm that GPX3 mRNA expression in adipose tissue correlates with BMI in humans. Cultivating 3T3-L1 pre-adipocytes in palmitate-containing medium followed by Se treatment attenuates insulin resistance with enhanced GPx3 and IR expression and adipocyte differentiation. However, feeding obese mice a selenium-enriched high-fat diet (SRHFD) only resulted in a modest increase in overall selenoprotein gene expression in WAT in mice with unaltered body weight development, glucose tolerance, and insulin resistance. While Se supplementation improved adipocyte morphology, it did not alter WAT insulin sensitivity. However, mice fed a SRHFD exhibited increased insulin content in the pancreas. Overall, while selenite protects against palmitate-induced insulin resistance in vitro, obesity impedes the effect of selenite on insulin action and adipose tissue metabolism in vivo.
KW  - selenite
KW  - insulin
KW  - adipose tissue
KW  - obesity
KW  - insulin resistance
Y1  - 2022
U6  - https://doi.org/10.3390/antiox11050862
SN  - 2076-3921
VL  - 11
SP  - 1
EP  - 16
PB  - MDPI
CY  - Basel, Schweiz
ET  - 5
ER  - 
TY  - JOUR
A1  - Aga-Barfknecht, Heja
A1  - Soultoukis, George A.
A1  - Stadion, Mandy
A1  - Garcia-Carrizo, Francisco
A1  - Jähnert, Markus
A1  - Gottmann, Pascal
A1  - Vogel, Heike
A1  - Schulz, Tim Julius
A1  - Schürmann, Annette
T1  - Distinct adipogenic and fibrogenic differentiation capacities of mesenchymal stromal cells from pancreas and white adipose tissue
JF  - International journal of molecular sciences
N2  - Pancreatic steatosis associates with beta-cell failure and may participate in the development of type-2-diabetes. Our previous studies have shown that diabetes-susceptible mice accumulate more adipocytes in the pancreas than diabetes-resistant mice. In addition, we have demonstrated that the co-culture of pancreatic islets and adipocytes affect insulin secretion. The aim of this current study was to elucidate if and to what extent pancreas-resident mesenchymal stromal cells (MSCs) with adipogenic progenitor potential differ from the corresponding stromal-type cells of the inguinal white adipose tissue (iWAT). miRNA (miRNome) and mRNA expression (transcriptome) analyses of MSCs isolated by flow cytometry of both tissues revealed 121 differentially expressed miRNAs and 1227 differentially expressed genes (DEGs). Target prediction analysis estimated 510 DEGs to be regulated by 58 differentially expressed miRNAs. Pathway analyses of DEGs and miRNA target genes showed unique transcriptional and miRNA signatures in pancreas (pMSCs) and iWAT MSCs (iwatMSCs), for instance fibrogenic and adipogenic differentiation, respectively. Accordingly, iwatMSCs revealed a higher adipogenic lineage commitment, whereas pMSCs showed an elevated fibrogenesis. As a low degree of adipogenesis was also observed in pMSCs of diabetes-susceptible mice, we conclude that the development of pancreatic steatosis has to be induced by other factors not related to cell-autonomous transcriptomic changes and miRNA-based signals.
KW  - MSCs
KW  - fatty pancreas
KW  - WAT
KW  - lineage commitment
KW  - transcriptomics
KW  - miRNAs
Y1  - 2022
U6  - https://doi.org/10.3390/ijms23042108
SN  - 1422-0067
VL  - 23
IS  - 4
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -