Insulin resistance in obese adolescents and adult men modifies the expression of proliferation related genes

Minchenko, О. H.; Viletska, Yulia M.; Minchenko, Dmytro O.; Davydov, Roman

doi:10.15407/ubj91.03.065

Cited by 2 publications

(2 citation statements)

References 47 publications

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“…Deletion of ANK2 in adipose tissue also increases glucose uptake and lipogenesis as a result of insufficient glucose transporter type 4 ( GLUT4 ) at the cell surface 21 . Additionally, SLC1A3 gene overexpression decreases the subcutaneous adipose tissue of obese adults without insulin resistance 22 . Loss of ALOX5 resulted in age‐related obesity with a series of metabolic defects, including fatty liver 23 .…”

Section: Discussionmentioning

confidence: 99%

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Interaction of environmental factors with the polygenic risk scores of thinness‐related genes in preventing obesity risk in middle‐aged adults: The KoGES

Zhou

Liu

Park

2023

J Human Nutrition Diet

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Background Some persons are genetically resistant to obesity, but only a few studies have evaluated thinness genes for preventing obesity. We aimed to investigate the association of polygenic variants with being underweight and their interaction with the lifestyles of middle‐aged and elderly persons and identify potential new genetic approaches for managing body weight. Methods In total, 58,701 participants aged 40–77 years were recruited from urban hospitals in Korea. Underweight (case) was defined as body mass index (BMI) < 18.5 kg m2 (n = 991) and normal weight (control, n = 21,921) was defined as 18.5 ≤ BMI < 23 kg m2. A genome‐wide association study was run to identify thinness‐related single nucleotide polymorphisms (SNPs) after adjustment for compound factors using Gplink. The generalised multifactor dimensionality reduction program was used to identify the genetic variants with SNP–SNP interactions. The polygenic risk score (PRS) was calculated by summing up the number of risk alleles in each SNP and classifying them into low‐, medium‐ and high‐PRS. Results The best model included the ANK2_rs7656666, CAST_rs28042, SLC1A3_rs928431867, CHST12_rs2906173, ALOX5_rs1051713, RGS6_rs17180754, ST8SIA5_rs79491311 and DCC_rs35721894 alleles. The participants with high‐PRS had a lower BMI (p < 0.0001) than those with low‐PRS and were 3.834 (2.58–5.70) times more likely to be underweight after multivariate adjustment (p < 0.001). The selected SNPs were correlated with each other and highly expressed in brain‐related genes. The genes with minor alleles of CAST_rs28042 and CHST12_rs2906173 exhibited a higher expression frequency in brain‐related tissues. PRS had significant interactions with protein, sodium, indigestible carbohydrates, calcium intake and exercise (p < 0.05), influencing the underweight state. People with a high‐PRS were more underweight than those with low‐PRS under high protein, sodium, high calcium, low indigestible carbohydrate intake and low exercise by 3.75, 3.88, 7.05, 3.18 and 3.80 times, respectively (p < 0.0001). Conclusions In conclusion, adults having a high‐PRS were significantly correlated with being underweight, especially in combination with a particular nutritional status. These results show the potential for thinness genes to be applied to personalised nutrition for preventing obesity through targeted gene therapy.

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Section: Discussionmentioning

confidence: 99%

“…21 Additionally, SLC1A3 gene overexpression decreases the subcutaneous adipose tissue of obese adults without insulin resistance. 22 Loss of ALOX5 resulted in age-related obesity with a series of metabolic defects, including fatty liver. 23 Moreover, the knockdown of RGS6 affected adult hippocampal neurogenesis.…”

Section: Discussionmentioning

confidence: 99%

Interaction of environmental factors with the polygenic risk scores of thinness‐related genes in preventing obesity risk in middle‐aged adults: The KoGES

Zhou

Liu

Park

2023

J Human Nutrition Diet

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Molecular Basis of the Development of Insulin Resistance in Obese Adolescent and Adult Men

Viletska¹

2022

Biotechnol. acta

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The aim of this work was to study the association between the expression of glucose metabolism related genes and insulin resistance, which expression is changed in obese adolescents and adult men with and without insulin resistance, for better understanding the molecular basis of the development of obesity complications and evaluation of possible contribution of these genes in development of insulin resistance. Methods. The expression level of genes related to glucose metabolism and their regulations was studied by real-time qPCR in adipose tissue and blood cells using SYBRGreen Mix and specific for each mRNA forward and reverse primers. Total RNA was extracted using TRIZOL reagent. For reverse transcription of mRNAs we used Thermo Scientific Verso cDNA Synthesis Kit (Germany). The values of mRNA expressions were normalized to the level of ACTB mRNA and represented as percent of control (100 %). Results. It was shown that in obese patients with insulin resistance the expression level of IRS1 (insulin receptor substrate 1), HK2 (hexokinase 2), PFKFB2 (6-phosphofructokinase/fructose-2,6-bisphosphatase 2) and PFKFB3 as well as circadian factors CLOCK and ARNTL genes in subcutaneous adipose tissue is significantly decreased as compared to obese men with normal sensitivity to insulin. At the same time, the development of insulin resistance in obese patients leads to up-regulation of PFKFB4, PER1, HSPA6, ALDH1A3, COL5A1, TIMP1, TIMP2, SPARC, and VCAN gene expressions in subcutaneous adipose tissue. The expression level of IGF1 (insulin-like growth factor 1) and IGFBP5 (IGF binding protein 5) as well as ENO1 (enolase 1) and ENO2 is down-regulated in the blood of obese adolescent with insulin resistance, but IGFBP2 and IGFBP7 gene expressions are significantly increased in these patients. Conclusions. The results of this investigation provide evidence that the development of insulin resistance in obese patients is associated with gene specific changes in the expression of many very important regulatory genes, which are endoplasmic reticulum stress responsible.

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Insulin resistance in obese adolescents and adult men modifies the expression of proliferation related genes

Cited by 2 publications

References 47 publications

Interaction of environmental factors with the polygenic risk scores of thinness‐related genes in preventing obesity risk in middle‐aged adults: The KoGES

Interaction of environmental factors with the polygenic risk scores of thinness‐related genes in preventing obesity risk in middle‐aged adults: The KoGES

Molecular Basis of the Development of Insulin Resistance in Obese Adolescent and Adult Men

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