Measure of expression of mitochondrial related genes in human mononuclear blood cells, adipose white tissue and smooth muscle cells

Fabricius, M.H.; Wilms, Line Kønig; Larsen, Jacob; Pedersen, Palle; Anthonsen, Stine; Kvetny, Jan

doi:10.1016/j.cca.2010.02.005

Cited by 4 publications

(6 citation statements)

References 19 publications

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“…Nevertheless, as the expression of other respiratory chain enzymes was not affected in either group, it seems that compared with SCAT the mitochondria of PM are much less prone to disturbances associated with obesity and T2DM. This is in contrast with the situation in healthy individuals, where the expression of mitochondria-related genes was reported to be comparable between mononuclear blood cells and white visceral adipose tissue (Fabricius et al 2010). Interestingly, when assessing the activity of respiratory chain enzymes in peripheral blood elements, we found, except of decreased activity of complex IV, an unexpected, albeit non-significant, increase in the activity of complex I (NQR).…”

Section: Discussioncontrasting

confidence: 99%

The Effect of Very-Low-Calorie Diet on Mitochondrial Dysfunction in Subcutaneous Adipose Tissue and Peripheral Monocytes of Obese Subjects with Type 2 Diabetes Mellitus

Urbanová¹,

Mráz²,

Ďurovcová³

et al. 2017

Physiol Res

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Mitochondrial dysfunction is a potentially important player in the development of insulin resistance and type 2 diabetes mellitus (T2DM). We investigated the changes of mRNA expression of genes encoding main enzymatic complexes of mitochondrial respiratory chain in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM) of 11 subjects with simple obesity (OB), 16 obese patients with T2DM and 17 healthy lean subjects (C) before and after very low-calorie diet (VLCD) using quantitative real time PCR. At baseline in SCAT, both T2DM and OB group had decreased mRNA expression of all investigated mitochondrial genes with the exception of 2 complex I (NDUFA 12) and complex IV (COX 4/1) enzymes in OB subjects. In contrast, in PM only the expression of complex I enzymes NDUFA 12 and MT-ND5 was reduced in both T2DM and OB subjects along with decreased expression of citrate synthase (CS) in T2DM group. Additionally, T2DM subjects showed reduced activity of pyruvate dehydrogenase and complex IV in peripheral blood elements. VLCD further decreased mRNA expression of CS and complex I (NT-ND5) and II (SDHA) enzymes in SCAT and complex IV (COX4/1) and ATP synthase in PM of T2DM group, while increasing the activity of complex IV in their peripheral blood elements. We conclude that impaired mitochondrial biogenesis and decreased activity of respiratory chain enzymatic complexes was present in SCAT and PM of obese and diabetic patients. VLCD improved metabolic parameters and ameliorated mitochondrial oxidative function in peripheral blood elements of T2DM subjects but had only minor and inconsistent effect on mitochondrial gene mRNA expression in SCAT and PM.

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Section: Discussioncontrasting

confidence: 99%

The Effect of Very-Low-Calorie Diet on Mitochondrial Dysfunction in Subcutaneous Adipose Tissue and Peripheral Monocytes of Obese Subjects with Type 2 Diabetes Mellitus

Urbanová¹,

Mráz²,

Ďurovcová³

et al. 2017

Physiol Res

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“…Another noteworthy finding in the present study is the demonstration of positive correlations between the investigated mitochondria-related genes, confirming they are part of a common regulatory pathway. To our knowledge, only few studies have investigated the correlation between regulators of mitochondrial function [ 38 ], but Fabricius et al had similar results with positive correlations between expressed mitochondria-related genes within specific tissue types [ 6 ]. They investigated expressions in smooth muscle tissue (uterus), white adipose tissue and blood of 17 persons and found different levels of expressions in different tissues.…”

Section: Discussionmentioning

confidence: 99%

“…The choice of mitochondria-related genes were based on the fact that these different genes reflect mitochondrial function differently [ 5 , 11 , 33 ], and due to former laboratory experience [ 6 , 34 ].…”

Section: Methodsmentioning

confidence: 99%

“…Examples of thyroid regulated mitochondria-related transcripts (genomic level) are the co-activators from the PGC-1 family [ 5 – 8 ], the transcription factors Nuclear Respiratory Factor 1 (NRF-1) or 2 (NRF-2) [ 5 , 9 ], mitochondrial Transcription Factor A (TFAM) [ 5 , 6 ] and the antioxidant enzymes Superoxide Dismutase 1–3 (SOD1-3) [ 10 , 11 ]. Expression of these mitochondria-related genes are all linked to mitochondrial biogenesis and function, and therefore, thyroid dysfunction may be associated with changes in these.…”

Section: Introductionmentioning

confidence: 99%

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Expressions of mitochondria-related genes in pregnant women with subclinical hypothyroidism, and expressions of miRNAs in maternal and cord blood

Stryhn,

Larsen,

Pedersen

et al. 2023

Thyroid Res

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Background Subclinical hypothyroidism in pregnancy and definition by upper thyrotropin (TSH) cutoff are controversial. As mitochondria are influenced by thyroid hormones, the purpose in this study was to measure expression of mitochondria-related genes in euthyroid and subclinical hypothyroid pregnant women to obtain more knowledge of potential metabolic consequences of maternal subclinical hypothyroidism. In addition, we wished to test if applied TSH-cutoff significantly changed our results of expressed gene-levels. Moreover, we aimed to identify potential microRNA-biomarkers for subclinical hypothyroidism – markers that could be traced to offspring as well. Methods From a cohort of at-term pregnant women undergoing planned cesarean section, 77 women had expression levels of the mitochondria-related genes Peroxisome Proliferator-activated Receptor-γ coactivator-1β (PGC-1β), mitochondrial Transcription Factor A (TFAM), Superoxide Dismutase 2 (SOD2) and Nuclear Respiratory Factor 2 (NRF-2) determined by qPCR from blood sampled in prior to delivery. Two TSH-cutoff levels defining subclinical hypothyroidism (> 3.0 and > 3.7 mIU/L) were applied for the procession of results, generating two data analyses of the same cohort. In 22 pairwise maternal-cord samples (subclinical hypothyroid/euthyroid-rate 0.5, TSH-cutoff > 3.0 mIU/L), microRNA-expressions (miRNA) were analyzed. Results All gene expressions were lower in the subclinical hypothyroid group regardless of applied TSH-cutoff, but insignificant except for PGC-1β at TSH cutoff > 3.0 mIU/L. Two miRNAs (hsa-let-7d-3p and hsa-miR-345-5p) were upregulated in blood from women and offspring (cord blood) with subclinical hypothyroidism. Conclusions A trend towards decreased mitochondrial gene expressions in subclinical hypothyroidism were demonstrated. The miRNAs hsa-let-7d-3p and hsa-miR-345-5p might be potential markers of maternal subclinical hypothyroidism. However, larger studies are needed to verify the findings.

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“…A RIN value above 7.0 was considered acceptable for analysis. We examined whole blood gene expressions of PGC-1α, PGC-1β, TFAM, NFE2L2, and SOD2 before HT and from the last post-HT visit after a one-year follow-up by reverse transcription (RT) quantitative Polymerase Chain Reaction (qPCR) as previously described by Fabricius et al [18]. ▶Table 1 presents the primer sequences used.…”

Section: Rna Purification and Rt-qpcrmentioning

confidence: 99%

Reduced Gene Expression of Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1α in Whole Blood in Euthyroid Patients One Year After Hemithyroidectomy for Benign Euthyroid Goiter

et al. 2019

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We have previously reported decreased thyroid function within the laboratory reference range and changes in mitochondrial function after hemithyroidectomy. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and coactivator-1β (PGC-1β) are key regulators of mitochondrial biogenesis and function. The aim was to examine the influence of hemithyroidectomy on the longitudinal change in mRNA expression of these genes. In addition, we measured longitudinal changes in mRNA expressions of the mitochoncrial-related genes nuclear factor erythroid-derived 2-like 2 (NFE2L2), mitochondrial transcription factor A (TFAM), and sodium dismutase 2 (SOD2). Twenty-eight patients were examined before and 1, 3, 6, and 12 months after hemithyroidectomy for benign euthyroid goiter. Thyroid stimulating hormone (TSH) and thyroid hormones were measured, and whole blood gene expression of PGC-1α, PGC-1β, NFE2L2, TFAM, and SOD2 was examined by reverse transcription quantitative Polymerase Chain Reaction. We used mixed effect regression models to investigate changes in gene expression with time. Averaged over all follow-up visits, TSH increased (p=0.001), tT3 declined (p=0.01), and fT4/tT3 ratio increased (p=0.03) over one-year follow-up, but fT4 remained unchanged. Averaged over all follow-up visits, whole blood PGC-1α levels (p<0.001) and SOD2 (p=0.009) levels declined, but PGC-1β, TFAM, and NFE2L2 did not change over one-year follow-up. The study demonstrates significant downregulation of whole blood PGC-1α and SOD2 gene expressions in hemithyroidectomized patients with a concomitant increase in TSH concentration within the reference range. Thus, hemithyroidectomized patients may likely have impaired mitochondrial function.

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Measure of expression of mitochondrial related genes in human mononuclear blood cells, adipose white tissue and smooth muscle cells

Cited by 4 publications

References 19 publications

The Effect of Very-Low-Calorie Diet on Mitochondrial Dysfunction in Subcutaneous Adipose Tissue and Peripheral Monocytes of Obese Subjects with Type 2 Diabetes Mellitus

The Effect of Very-Low-Calorie Diet on Mitochondrial Dysfunction in Subcutaneous Adipose Tissue and Peripheral Monocytes of Obese Subjects with Type 2 Diabetes Mellitus

Expressions of mitochondria-related genes in pregnant women with subclinical hypothyroidism, and expressions of miRNAs in maternal and cord blood

Reduced Gene Expression of Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1α in Whole Blood in Euthyroid Patients One Year After Hemithyroidectomy for Benign Euthyroid Goiter

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