Expression Patterns of SIRT1, SIRT3, and TFAM in Adipose Tissue: Associations with Adiposity Indices and Insulin Resistance in Women
Abstract
Objectives: Obesity is linked to metabolic dysfunction, with mitochondrial regulators such as SIRT1, SIRT3, and TFAM playing key roles in adipose tissue health. This study examined the expression of these genes in subcutaneous and visceral adipose tissues of obese and normal-weight women, and their associations with adiposity indices and insulin resistance.
Methods: Forty-six women (22 obese, 24 normal-weight) were enrolled. Anthropometric, metabolic, and biochemical parameters were measured. mRNA levels of SIRT1, SIRT3, and TFAM were assessed in adipose tissue samples using quantitative real-time PCR.
Results: Obese women had significantly higher adiposity indices and insulin resistance markers. SIRT1 expression in subcutaneous adipose tissue and SIRT3 expression in visceral adipose tissue were lower in obese women compared to controls. SIRT1 and SIRT3 transcript levels showed significant inverse correlations with several adiposity indices and insulin resistance measures. TFAM expression did not differ significantly between groups but was inversely associated with metabolic risk factors in visceral fat.
Conclusions:
Reduced SIRT1 and SIRT3 expression in adipose tissue is associated with greater adiposity and insulin resistance in obese women, suggesting a potential role for these genes in obesity-related metabolic disturbances.
1. Narani MS, Vatannejad A, Kheirollahi A, Teimouri M, Bayat S, Jadidzadeh F. Changes of biochemical parameters in normal weight and overweight/obese women with polycystic ovary Syndrome. Acta Biochim Iran. 2023;1(3). https://doi.org/10.18502/abi.v1i3.14547
2. Emamgholipour S, Esmaeili F, Shabani M, Hasanpour SZ, Pilehvari M, Zabihi-Mahmoudabadi H, et al. Alterations of SOCS1 and SOCS3 transcript levels, but not promoter methylation levels in subcutaneous adipose tissues in obese women. BMC Endocr Disord. 2023;23(1):7. https://doi.org/10.1186/s12902-022-01247-5
3. Ghahremani H, Bahramzadeh A, Bolandnazar K, Emamgholipor S, Hosseini H, Meshkani R. Resveratrol as a potential protective compound against metabolic inflammation. Acta Biochim Iran. 2023;1(2). https://doi.org/10.18502/abi.v1i2.14101
4. Fadaei R. Adipokines as a link between adipose tissue with inflammation and insulin resistance in cardiometabolic diseases. Acta Biochim Iran. 2023;1(3):112-8. https://doi.org/10.18502/abi.v1i3.14546
5. Nijhawan P, Behl T. Role of sirtuins in obesity. Obes Med. 2020;17:100156. https://doi.org/10.1016/j.obmed.2019.100156
6. Kielbowski K, Bratborska AW, Bakinowska E, Pawlik A. Sirtuins as therapeutic targets in diabetes. Expert Opin Ther Targets. 2025;29(3):117-35. https://doi.org/10.1080/14728222.2025.2482563
7. Parihar P, Solanki I, Mansuri ML, Parihar MS. Mitochondrial sirtuins: emerging roles in metabolic regulations, energy homeostasis and diseases. Exp Gerontol. 2015;61:130-41. https://doi.org/10.1016/j.exger.2014.12.004
8. Yuan Y, Cruzat VF, Newsholme P, Cheng J, Chen Y, Lu Y. Regulation of SIRT1 in aging: Roles in mitochondrial function and biogenesis. Mech Ageing Dev. 2016;155:10-21. https://doi.org/10.1016/j.mad.2016.02.003
9. Bause AS, Haigis MC. SIRT3 regulation of mitochondrial oxidative stress. Exp Gerontol. 2013;48(7):634-9. https://doi.org/10.1016/j.exger.2012.08.007
10. Choudhury M, Jonscher KR, Friedman JE. Reduced mitochondrial function in obesity-associated fatty liver: SIRT3 takes on the fat. Aging (Albany NY). 2011;3(2):175-8. https://doi.org/10.18632/aging.100289
11. Pardo PS, Boriek AM. SIRT1 Regulation in Ageing and Obesity. Mech Ageing Dev. 2020;188:111249. https://doi.org/10.1016/j.mad.2020.111249
12. Maghbooli Z, Emamgholipour S, Aliakbar S, Amini M, Gorgani-Firuzjaee S, Hossein-Nezhad A. Differential expressions of SIRT1, SIRT3, and SIRT4 in peripheral blood mononuclear cells from patients with type 2 diabetic retinopathy. Arch Physiol Biochem. 2020;126(4):363-8. https://doi.org/10.1080/13813455.2018.1543328
13. Sadeghabadi ZA, Nourbakhsh M, Pasalar P, Emamgholipour S, Golestani A, Larijani B, et al. Reduced gene expression of sirtuins and active AMPK levels in children and adolescents with obesity and insulin resistance. Obes Res Clin Pract. 2018;12(2):167-73. https://doi.org/10.1016/j.orcp.2017.10.004
14. Jannat Ali Pour N, Zabihi-Mahmoudabadi H, Ebrahimi R, Yekaninejad MS, Hashemnia SMR, Meshkani R, et al. Principal component analysis of adipose tissue gene expression of lipogenic and adipogenic factors in obesity. BMC Endocr Disord. 2023;23(1):94. https://doi.org/10.1186/s12902-023-01347-w
15. Clark SJ, Falchi M, Olsson B, Jacobson P, Cauchi S, Balkau B, et al. Association of sirtuin 1 (SIRT1) gene SNPs and transcript expression levels with severe obesity. Obesity (Silver Spring). 2012;20(1):178-85. https://doi.org/10.1038/oby.2011.200
16. Mariani S, Di Giorgio MR, Rossi E, Tozzi R, Contini S, Bauleo L, et al. Blood SIRT1 shows a coherent association with leptin and adiponectin in relation to the degree and distribution of adiposity: a study in obesity, normal weight and anorexia nervosa. Nutrients. 2020;12(11):3506. https://doi.org/10.3390/nu12113506
17. Mariani S, Fiore D, Basciani S, Persichetti A, Contini S, Lubrano C, et al. Plasma levels of SIRT1 associate with non-alcoholic fatty liver disease in obese patients. Endocrine. 2015;49(3):711-6. https://doi.org/10.1007/s12020-014-0465-x
18. Boyle KE, Newsom SA, Janssen RC, Lappas M, Friedman JE. Skeletal muscle MnSOD, mitochondrial complex II, and SIRT3 enzyme activities are decreased in maternal obesity during human pregnancy and gestational diabetes mellitus. J Clin Endocrinol Metab. 2013;98(10):E1601-9. https://doi.org/10.1210/jc.2013-1943
19. Du Y, Huo Y, Yang Y, Lin P, Liu W, Wang Z, et al. Role of sirtuins in obesity and osteoporosis: molecular mechanisms and therapeutic targets. Cell Commun Signal. 2025;23(1):20. https://doi.org/10.1186/s12964-024-02025-7
20. Boutant M, Canto C. SIRT1 metabolic actions: Integrating recent advances from mouse models. Mol Metab. 2014;3(1):5-18. https://doi.org/10.1016/j.molmet.2013.10.006
21. Guo X, Yan F, Li J, Zhang C, Su H, Bu P. SIRT3 Ablation Deteriorates Obesity-Related Cardiac Remodeling by Modulating ROS-NF-kappaB-MCP-1 Signaling Pathway. J Cardiovasc Pharmacol. 2020;76(3):296-304. https://doi.org/10.1097/FJC.0000000000000877
22. Koh J-H, Kim Y-W, Seo D-Y, Sohn T-S. Mitochondrial TFAM as a signaling regulator between cellular organelles: a perspective on metabolic diseases. Diabetes Metab J 2021;45(6):853-65. https://doi.org/10.4093/dmj.2021.0138
2. Emamgholipour S, Esmaeili F, Shabani M, Hasanpour SZ, Pilehvari M, Zabihi-Mahmoudabadi H, et al. Alterations of SOCS1 and SOCS3 transcript levels, but not promoter methylation levels in subcutaneous adipose tissues in obese women. BMC Endocr Disord. 2023;23(1):7. https://doi.org/10.1186/s12902-022-01247-5
3. Ghahremani H, Bahramzadeh A, Bolandnazar K, Emamgholipor S, Hosseini H, Meshkani R. Resveratrol as a potential protective compound against metabolic inflammation. Acta Biochim Iran. 2023;1(2). https://doi.org/10.18502/abi.v1i2.14101
4. Fadaei R. Adipokines as a link between adipose tissue with inflammation and insulin resistance in cardiometabolic diseases. Acta Biochim Iran. 2023;1(3):112-8. https://doi.org/10.18502/abi.v1i3.14546
5. Nijhawan P, Behl T. Role of sirtuins in obesity. Obes Med. 2020;17:100156. https://doi.org/10.1016/j.obmed.2019.100156
6. Kielbowski K, Bratborska AW, Bakinowska E, Pawlik A. Sirtuins as therapeutic targets in diabetes. Expert Opin Ther Targets. 2025;29(3):117-35. https://doi.org/10.1080/14728222.2025.2482563
7. Parihar P, Solanki I, Mansuri ML, Parihar MS. Mitochondrial sirtuins: emerging roles in metabolic regulations, energy homeostasis and diseases. Exp Gerontol. 2015;61:130-41. https://doi.org/10.1016/j.exger.2014.12.004
8. Yuan Y, Cruzat VF, Newsholme P, Cheng J, Chen Y, Lu Y. Regulation of SIRT1 in aging: Roles in mitochondrial function and biogenesis. Mech Ageing Dev. 2016;155:10-21. https://doi.org/10.1016/j.mad.2016.02.003
9. Bause AS, Haigis MC. SIRT3 regulation of mitochondrial oxidative stress. Exp Gerontol. 2013;48(7):634-9. https://doi.org/10.1016/j.exger.2012.08.007
10. Choudhury M, Jonscher KR, Friedman JE. Reduced mitochondrial function in obesity-associated fatty liver: SIRT3 takes on the fat. Aging (Albany NY). 2011;3(2):175-8. https://doi.org/10.18632/aging.100289
11. Pardo PS, Boriek AM. SIRT1 Regulation in Ageing and Obesity. Mech Ageing Dev. 2020;188:111249. https://doi.org/10.1016/j.mad.2020.111249
12. Maghbooli Z, Emamgholipour S, Aliakbar S, Amini M, Gorgani-Firuzjaee S, Hossein-Nezhad A. Differential expressions of SIRT1, SIRT3, and SIRT4 in peripheral blood mononuclear cells from patients with type 2 diabetic retinopathy. Arch Physiol Biochem. 2020;126(4):363-8. https://doi.org/10.1080/13813455.2018.1543328
13. Sadeghabadi ZA, Nourbakhsh M, Pasalar P, Emamgholipour S, Golestani A, Larijani B, et al. Reduced gene expression of sirtuins and active AMPK levels in children and adolescents with obesity and insulin resistance. Obes Res Clin Pract. 2018;12(2):167-73. https://doi.org/10.1016/j.orcp.2017.10.004
14. Jannat Ali Pour N, Zabihi-Mahmoudabadi H, Ebrahimi R, Yekaninejad MS, Hashemnia SMR, Meshkani R, et al. Principal component analysis of adipose tissue gene expression of lipogenic and adipogenic factors in obesity. BMC Endocr Disord. 2023;23(1):94. https://doi.org/10.1186/s12902-023-01347-w
15. Clark SJ, Falchi M, Olsson B, Jacobson P, Cauchi S, Balkau B, et al. Association of sirtuin 1 (SIRT1) gene SNPs and transcript expression levels with severe obesity. Obesity (Silver Spring). 2012;20(1):178-85. https://doi.org/10.1038/oby.2011.200
16. Mariani S, Di Giorgio MR, Rossi E, Tozzi R, Contini S, Bauleo L, et al. Blood SIRT1 shows a coherent association with leptin and adiponectin in relation to the degree and distribution of adiposity: a study in obesity, normal weight and anorexia nervosa. Nutrients. 2020;12(11):3506. https://doi.org/10.3390/nu12113506
17. Mariani S, Fiore D, Basciani S, Persichetti A, Contini S, Lubrano C, et al. Plasma levels of SIRT1 associate with non-alcoholic fatty liver disease in obese patients. Endocrine. 2015;49(3):711-6. https://doi.org/10.1007/s12020-014-0465-x
18. Boyle KE, Newsom SA, Janssen RC, Lappas M, Friedman JE. Skeletal muscle MnSOD, mitochondrial complex II, and SIRT3 enzyme activities are decreased in maternal obesity during human pregnancy and gestational diabetes mellitus. J Clin Endocrinol Metab. 2013;98(10):E1601-9. https://doi.org/10.1210/jc.2013-1943
19. Du Y, Huo Y, Yang Y, Lin P, Liu W, Wang Z, et al. Role of sirtuins in obesity and osteoporosis: molecular mechanisms and therapeutic targets. Cell Commun Signal. 2025;23(1):20. https://doi.org/10.1186/s12964-024-02025-7
20. Boutant M, Canto C. SIRT1 metabolic actions: Integrating recent advances from mouse models. Mol Metab. 2014;3(1):5-18. https://doi.org/10.1016/j.molmet.2013.10.006
21. Guo X, Yan F, Li J, Zhang C, Su H, Bu P. SIRT3 Ablation Deteriorates Obesity-Related Cardiac Remodeling by Modulating ROS-NF-kappaB-MCP-1 Signaling Pathway. J Cardiovasc Pharmacol. 2020;76(3):296-304. https://doi.org/10.1097/FJC.0000000000000877
22. Koh J-H, Kim Y-W, Seo D-Y, Sohn T-S. Mitochondrial TFAM as a signaling regulator between cellular organelles: a perspective on metabolic diseases. Diabetes Metab J 2021;45(6):853-65. https://doi.org/10.4093/dmj.2021.0138
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| Issue | Vol 2 No 4 (2024) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/abi.v2i4.19111 | |
| Keywords | ||
| SIRT1 SIRT3 TFAM subcutaneous visceral adipose tissue obesity | ||
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How to Cite
1.
Mohassel Azadi S, Shanaki , M, Zabihi-Mahmoudabadi H, Emamgholipour S. Expression Patterns of SIRT1, SIRT3, and TFAM in Adipose Tissue: Associations with Adiposity Indices and Insulin Resistance in Women. ABI. 2024;2(4):227-233.
