Adiponectin and Serine/Threonine Kinase Akt Modulation by Triiodothyronine and/or LY294002 in 3T3‐L1 Adipocytes

Oliveira, Mauro Dal Secco de; Rodrigues, Bruna Moretto; Olímpio, Regiane Marques Castro; Mathias, Lucas Solla; Síbio, Maria Teresa De; Moretto, Fernanda Cristina Fontes; Graceli, Jones Bernardes; Nogueira, Célia Regina

doi:10.1002/lipd.12135

Cited by 10 publications

(4 citation statements)

References 40 publications

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“…Serum adiponectin, insulin sensitivity, and thyroid status might be linked to each other, which in turn may influence metabolic milieu and cardiovascular health through either disruption in lipemic equilibrium or other mechanisms. de Oliveira et al ( 2019) found that T3 acts on the PI3K/Akt signaling pathway resulting in the differentiation of various cell lines, including adipocytes and thus resulting in increased adiponectin levels [27]. It also acts by enhancing the transcription of various adipokine genes.…”

Section: Discussionmentioning

confidence: 99%

Levothyroxine Therapy and Predictors of Cardiovascular Risk in Clinical Hypothyroidism: A Prospective Cohort Study

Maiti¹,

Mohanty²,

Mishra³

et al. 2022

Cureus

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BackgroundHypothyroidism is associated with hypoadiponectinemia, insulin resistance, and increased cardiovascular risk. The association of adiponectin, insulin resistance, and future cardiovascular risk in clinical hypothyroidism and the effect of levothyroxine are non-conclusive because of the contradictory results. The present prospective cohort study has been conducted to evaluate the effect of levothyroxine on serum adiponectin, insulin resistance, and cardiovascular risk in patients with clinical hypothyroidism. MethodsSixty patients with clinical hypothyroidism who were prescribed levothyroxine were recruited following selection criteria and changes in Zulewski's score, glycemic parameters, homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), lipid profile, serum adiponectin, serum high-sensitivity C-reactive protein (hs-CRP), cardiovascular risk indices, and Framingham risk score were assessed 12 weeks post-levothyroxine therapy. Receiver operating characteristic (ROC) analysis was done to detect the cut-off for adiponectin levels to differentiate between responders and non-responders. Neural network models were created to predict the risk of cardiovascular morbidity. ResultsPost-levothyroxine therapy, there was a significant improvement in body mass index (BMI) (p = 0.025), diastolic blood pressure (p = 0.021), Zulewski's score (p < 0.001), serum insulin (p = 0.005), fasting sugar (p < 0.001), serum adiponectin (p < 0.001), thyroid profile (p < 0.001), total cholesterol (p < 0.001), low-density lipoprotein (p < 0.001), high-density lipoprotein (p = 0.007), triglycerides (p = 0.002), and subcutaneous fat (p = 0.015). Serum adiponectin showed significant improvement in hypothyroid patients compared to euthyroid individuals (mean difference: -2.21; 95% CI: -2.52 to -1.91; p < 0.001). Mean difference in insulin resistance (HOMA-IR: 0.3, p < 0.001; QUICKI: -0.002, p < 0.001) and cardiovascular risk (atherogenic index: 0.12, p = 0.04; coronary risk index: 0.14, p = 0.038; Framingham risk score: 0.65, p = 0.041) also showed improvement. Serum adiponectin and thyroid-stimulating hormone levels were directly correlated with insulin resistance and cardiovascular risk scores. ConclusionThe reduced serum adiponectin level and increased cardiovascular risk in clinical hypothyroidism were improved with hormone replacement, and serum adiponectin level was found to be a good prognostic marker for the treatment response.

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Section: Discussionmentioning

confidence: 99%

Levothyroxine Therapy and Predictors of Cardiovascular Risk in Clinical Hypothyroidism: A Prospective Cohort Study

Maiti¹,

Mohanty²,

Mishra³

et al. 2022

Cureus

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“…Co-stimulation experiments were performed with the NF-κB inhibitor BAY-11 (5 µM), the STAT3 inhibitor S3I-201 (50 µM), the selective MAPK inhibitor SB239063 (5 µM), the MEK-1/-2 inhibitor U0126 (5 µM) and the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (5 µM) (all purchased from Merck and Sigma-Aldrich), applying doses similar to those reported in the literature. 30–34…”

Section: Methodsmentioning

confidence: 99%

“…Co-stimulation experiments were performed with the NF-jB inhibitor BAY-11 (5 mM), the STAT3 inhibitor S3I-201 (50 mM), the selective MAPK inhibitor SB239063 (5 mM), the MEK-1/-2 inhibitor U0126 (5 mM) and the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (5 mM) (all purchased from Merck and Sigma-Aldrich), applying doses similar to those reported in the literature. [30][31][32][33][34] Isolation of mRNA and quantitative real-time PCR analysis of murine CAMP mRNA expression in adipose tissues of mice and in murine 3T3-L1 adipocytes Gonadal and subcutaneous adipose tissue compartments were resected from wild type C57BL/6N mice (sacrificed for organ samples conformable to §4 Abs. 3 Tierschutzgesetz).…”

Section: Adipocyte Cell Culture and Stimulation Experimentsmentioning

confidence: 99%

Regulation of CAMP (cathelicidin antimicrobial peptide) expression in adipocytes by TLR 2 and 4

et al. 2021

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Recent data argue for a pro-inflammatory role of CAMP (cathelicidin antimicrobial peptide) in adipocytes and adipose tissue (AT) and for regulatory circuits involving TLRs. In order to investigate regulatory effects of TLR2 and TLR4, 3T3-L1 adipocytes were stimulated with TLR2 agonistic lipopeptide MALP-2 and with TLR4 agonist LPS in presence or absence of signal transduction inhibitors. CAMP gene expression was analysed by quantitative real-time PCR in adipocytes and in murine AT compartments and cellular subfractions. CAMP expression was higher in gonadal than in subcutaneous AT and there was a gender-specific effect with higher levels in males. Adipocytes had higher CAMP expression than the stroma-vascular cell (SVC) fraction. MALP-2 up-regulated CAMP expression significantly, mediated by STAT3 and PI3K and potentially (non-significant trend) by NF-κB and MAPK, but not by raf-activated MEK-1/-2. Moreover, LPS proved to act as a potent inducer of CAMP via NF-κB, PI3K and STAT3, whereas specific inhibition of MAPK and MEK-1/-2 had no effect. In conclusion, activation of TLR2 and TLR4 by classical ligands up-regulates adipocyte CAMP expression involving classical signal transduction elements. These might represent future drug targets for pharmacological modulation of CAMP expression in adipocytes, especially in the context of metabolic and infectious diseases.

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“…It has been reported that different target organs show different sensitivities to thyroid hormone [ 11 ]. Adipose tissue, as one of the most important target organs of thyroid hormone, is capable of modulating physiological functions by synthesizing and releasing adipokines, such as adiponectin [ 12 – 14 ]. T3 and adiponectin play important roles in controlling normal metabolic functions.…”

Section: Introductionmentioning

confidence: 99%

Subcutaneous adipose tissue alteration in aging process associated with thyroid hormone signaling

Zhang,

Zhu,

et al. 2023

BMC Med Genomics

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Background Functional changes in subcutaneous adipose tissue (SAT) occur earlier in the aging process and play an important role in the occurrence and development of age-related metabolic diseases. The mechanism of this phenomenon is still unclear, and the change in adipose tissue with age is poorly understood. Methods We used transcriptome sequencing (RNA seq) to screen differentially expressed genes at the mRNA level, and analyzed the functional characteristics of the differential genes through GO and KEGG analysis in human SAT of all ages. In order to clarify the specific mechanism of the functional change, we analyzed the chromatin accessibility in the promoter region in the same SAT used in the RNA seq by the assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) and obtained the functional genes in SAT changed with age. To verify these changes, we enlarged our sample content of human SAT. The primary mice adipocytes were extracted and stimulated by thyroid hormone of different concentration to construct an animal model, and the expression of the genes were determined through real-time Polymerase Chain Reaction(RT-PCR). The oxygen consumption test and immunofluorescence staining were used to determine the mitochondrial function of SAT. Results RNA-seq showed characteristic gene expression of young and old human SAT, in which 331 genes were up-regulated and 349 genes were down-regulated. ATAC-seq, RNA-seq, combined with the mouse prediction model, determined the functional changed characteristics of seven genes. All these genes expressed differently in SAT of different ages, in which, NCF1, NLRP3, DUOX1 showed positive correlation with age; The expression of IFI30, P2RX1, P2RX6, PRODH, however, decreased with age. And all these genes showed dose dependent alternations under treatment of triiodothyroxine in mice SAT. The oxygen consumption rate revealed significant changes of the mitochondrial function and ROS accumulation in human SAT of different ages. Conclusion In elderly individuals, the function, in addition to distribution, of SAT undergoes significant changes, primarily in mitochondria, which may be due to insensitivity to thyroid hormone signaling. These results identified seven novel genes regulated by thyroid hormone, exhibiting significant changes in SAT of different age, and are probably related to the dysfunction of the aged SAT due to the mitochondrial damage and ROS accumulation.

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Adiponectin and Serine/Threonine Kinase Akt Modulation by Triiodothyronine and/or LY294002 in 3T3‐L1 Adipocytes

Cited by 10 publications

References 40 publications

Levothyroxine Therapy and Predictors of Cardiovascular Risk in Clinical Hypothyroidism: A Prospective Cohort Study

Levothyroxine Therapy and Predictors of Cardiovascular Risk in Clinical Hypothyroidism: A Prospective Cohort Study

Regulation of CAMP (cathelicidin antimicrobial peptide) expression in adipocytes by TLR 2 and 4

Subcutaneous adipose tissue alteration in aging process associated with thyroid hormone signaling

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