The Impact of Gastric Bypass on Telomere Length and Shelterin Complex Gene Expression: 6 Months Prospective Study

2021 ◽  
Author(s):  
Caroline Rossi Welendorf ◽  
Carolina Ferreira Nicoletti ◽  
Natália Yumi Noronha ◽  
Flávia Campos Ferreira ◽  
Letícia Santana Wolf ◽  
...  
2019 ◽  
Vol 60 (4) ◽  
pp. 361-367 ◽  
Author(s):  
Guo‐Qiao Zheng ◽  
Guang‐Hui Zhang ◽  
Han‐Tian Wu ◽  
Yu‐Ting Tu ◽  
Wei Tian ◽  
...  

2021 ◽  
Author(s):  
Matthew D. Barberio ◽  
G. Lynis Dohm ◽  
Walter J. Pories ◽  
Natalie A. Gadaleta ◽  
Joseph A. Houmard ◽  
...  

AbstractRoux-en-Y gastric bypass (RYGB) is an effective treatment for type 2 diabetes mellitus (T2DM) which can result in remission of clinical symptoms, yet mechanisms for improved skeletal muscle health are poorly understood. We sought to define the impact of existing T2DM on RYGB-induced muscle transcriptome changes.MethodsVastus lateralis biopsy transcriptomes were generated pre- and 1-yr post-RYGB in black adult females with (T2D; n = 5, age=51±6 yr, BMI=53.0±5.8 kg/m2) and without (CON; n = 7,43±6 yr,51.0±9.2 kg/m2) T2DM. Insulin, glucose, and HOMA-IR were measured in blood at the same time points. ANCOVA detected differentially expressed genes (p< 0.01, Fold change<|1.2|), which were used to identify enriched biological pathways.ResultsPre-RYGB, 95 probes were downregulated with T2D including subunits of mitochondrial complex I. Post-RYGB, the T2D group had normalized gene expression when compared to their non-diabetic counterparts with only 3 probes remaining significantly different. In the T2D, we identified 52 probes upregulated from pre- to post-RYGB, including NDFUB7 and NDFUA1.ConclusionBlack females with T2DM show extensive down regulation of genes across aerobic metabolism pathways prior to RYGB, which resolves 1 year post-RYGB and is related to improvements in clinical markers. These data support efficacy of RYGB for improving skeletal muscle health, especially in patients with T2DM.


2021 ◽  
Vol 12 ◽  
Author(s):  
Matthew D. Barberio ◽  
G. Lynis Dohm ◽  
Walter J. Pories ◽  
Natalie A. Gadaleta ◽  
Joseph A. Houmard ◽  
...  

IntroductionRoux-en-Y gastric bypass (RYGB) is an effective treatment for type 2 diabetes mellitus (T2DM) that can result in remission of clinical symptoms, yet mechanisms for improved skeletal muscle health are poorly understood. We sought to define the impact of existing T2DM on RYGB-induced muscle transcriptome changes.MethodsVastus lateralis biopsy transcriptomes were generated pre- and 1-year post-RYGB in black adult females with (T2D; n = 5, age = 51 ± 6 years, BMI = 53.0 ± 5.8 kg/m2) and without (CON; n = 7, 43 ± 6 years, 51.0 ± 9.2 kg/m2) T2DM. Insulin, glucose, and HOMA-IR were measured in blood at the same time points. ANCOVA detected differentially expressed genes (p &lt; 0.01, fold change &lt; |1.2|), which were used to identify enriched biological pathways.ResultsPre-RYGB, 95 probes were downregulated with T2D including subunits of mitochondrial complex I. Post-RYGB, the T2D group had normalized gene expression when compared to their non-diabetic counterparts with only three probes remaining significantly different. In the T2D, we identified 52 probes upregulated from pre- to post-RYGB, including NDFUB7 and NDFUA1.ConclusionBlack females with T2DM show extensive downregulation of genes across aerobic metabolism pathways prior to RYGB, which resolves 1 year post-RYGB and is related to improvements in clinical markers. These data support efficacy of RYGB for improving skeletal muscle health, especially in patients with T2DM.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 289-LB
Author(s):  
M. AGOSTINA SANTORO ◽  
JOSEPH BRANCALE ◽  
JILL CARMODY GARRISON ◽  
SRIRAM MACHINENI ◽  
SCOTT A. LAJOIE ◽  
...  

2020 ◽  
Vol 117 (48) ◽  
pp. 30639-30648
Author(s):  
Dan Hu ◽  
Emily C. Tjon ◽  
Karin M. Andersson ◽  
Gabriela M. Molica ◽  
Minh C. Pham ◽  
...  

IL-17–producing Th17 cells are implicated in the pathogenesis of rheumatoid arthritis (RA) and TNF-α, a proinflammatory cytokine in the rheumatoid joint, facilitates Th17 differentiation. Anti-TNF therapy ameliorates disease in many patients with rheumatoid arthritis (RA). However, a significant proportion of patients do not respond to this therapy. The impact of anti-TNF therapy on Th17 responses in RA is not well understood. We conducted high-throughput gene expression analysis of Th17-enriched CCR6+CXCR3−CD45RA−CD4+T (CCR6+T) cells isolated from anti-TNF–treated RA patients classified as responders or nonresponders to therapy. CCR6+T cells from responders and nonresponders had distinct gene expression profiles. Proinflammatory signaling was elevated in the CCR6+T cells of nonresponders, and pathogenic Th17 signature genes were up-regulated in these cells. Gene set enrichment analysis on these signature genes identified transcription factor USF2 as their upstream regulator, which was also increased in nonresponders. Importantly, short hairpin RNA targetingUSF2in pathogenic Th17 cells led to reduced expression of proinflammatory cytokines IL-17A, IFN-γ, IL-22, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as transcription factor T-bet. Together, our results revealed inadequate suppression of Th17 responses by anti-TNF in nonresponders, and direct targeting of the USF2-signaling pathway may be a potential therapeutic approach in the anti-TNF refractory RA.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Aaron L. Slusher ◽  
Tiffany M. Zúñiga ◽  
Edmund O. Acevedo

Age-related elevations in proinflammatory cytokines, known as inflamm-aging, are associated with shorter immune cell telomere lengths. Purpose. This study examined the relationship of plasma PTX3 concentrations, a biomarker of appropriate immune function, with telomere length in 15 middle-aged (40-64 years) and 15 young adults (20-31 years). In addition, PBMCs were isolated from middle-aged and young adults to examine their capacity to express a key mechanistic component of telomere length maintenance, human telomerase reverse transcriptase (hTERT), following ex vivo cellular stimulation. Methods. Plasma PTX3 and inflammatory cytokines (i.e., IL-6, IL-10, TGF-β, and TNF-α), PBMC telomere lengths, and PBMC hTERT gene expression and inflammatory protein secretion following exposure to LPS, PTX3, and PTX3+LPS were measured. Results. Aging was accompanied by the accumulation of centrally located visceral adipose tissue, without changes in body weight and BMI, and alterations in the systemic inflammatory milieu (decreased plasma PTX3 and TGF-β; increased TNF-α (p≤0.050)). In addition, shorter telomere lengths in middle-aged compared to young adults (p=0.011) were negatively associated with age, body fat percentages, and plasma TNF-α (r=−0.404, p=0.027; r=−0.427, p=0.019; and r=−0.323, p=0.041, respectively). Finally, the capacity of PBMCs to increase hTERT gene expression following ex vivo stimulation was impaired in middle-aged compared to young adults (p=0.033) and negatively associated with telomere lengths (r=0.353, p=0.028). Conclusions. Proinflammation and the impaired hTERT gene expression capacity of PBMCs may contribute to age-related telomere attrition and disease.


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