Obesity, Insulin Resistance and Dysregulation of the mTOR Signalling Pathway in Hidradenitis Suppurativa
DOI:
https://doi.org/10.3889/oamjms.2026.12113Keywords:
hidradenitis suppurativa, obesity, insulin resistance, IHS4, mTOR, metforminAbstract
BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent painful nodules, abscesses, and draining tunnels, with a predilection for intertriginous regions.
AIM: We aimed to review dysregulation of mTOR signalling pathway based on the latest relevant scientific studies.
METHODS: This literature review explores the association between HS, obesity, insulin resistance, and the dysregulation of mTOR signalling pathway. Additionally, research investigating the effects of therapeutic strategies, such as metformin and its influence on clinical outcomes in HS patients, was analyzed.
RESULTS: Obesity is considered a predisposing factor for the development of insulin resistance and type 2 diabetes, both of which influence the IHS4 (International Hidradenitis Suppurativa Severity Score System) score in HS patients. The prevalence of insulin resistance among HS patients is 43.4%. Studies have shown that metformin significantly reduces inflammatory cytokines, chemokines, and the expression of genes associated with glycolytic processes. In vitro analyses suggest that these effects are mediated through the modulations of the NLRP3 inflammasome and mTOR signalling pathway.
CONCLUSION: A holistic approach to HS treatment, including the management of obesity and insulin resistance, significantly improves disease progression. The use of metformin as an adjunct therapy in standard treatment protocols has the potential to improve IHS4 scores in obese patients.
Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Zouboulis CC, Del Marmol V, Mrowietz U, Bechara FG, Giamarellos-Bourboulis EJ, Ingram JR, et al. Hidradenitis suppurativa/acne inversa: criteria for diagnosis, severity assessment, classification and disease evaluation. Dermatology. 2015;231(2):184-90. https://doi.org/10.1159/000431175 PMid:26139027 DOI: https://doi.org/10.1159/000431175
Jemec GBE. Clinical practice. Hidradenitis suppurativa. N Engl J Med. 2012;366(2):158-64. https://doi.org/10.1056/NEJMcp1014163 PMid:22236226 DOI: https://doi.org/10.1056/NEJMcp1014163
Zouboulis CC, Tzellos T, Kyrgidis A, Jemec GBE, Bechara FG, Giamarellos-Bourboulis EJ, et al. Development and validation of the International Hidradenitis Suppurativa Severity Score System (IHS4), a novel dynamic scoring system to assess HS severity. Br J Dermatol. 2017;177(5):1401-9. https://doi.org/10.1111/bjd.15748 PMid:28636793 DOI: https://doi.org/10.1111/bjd.15748
Sartorius K, Emtestam L, Jemec GBE, Lapins J. Objective scoring of hidradenitis suppurativa reflecting the role of tobacco smoking and obesity. Br J Dermatol. 2009;161(4):831-9. https://doi.org/10.1111/j.1365-2133.2009.09198.x PMid:19438453 DOI: https://doi.org/10.1111/j.1365-2133.2009.09198.x
van Straalen KR, Prens EP, Gudjonsson JE. Insights into hidradenitis suppurativa. J Allergy Clin Immunol. 2022;149(4):1150-61. https://doi.org/10.1016/j.jaci.2022.02.003 PMid:35189127 DOI: https://doi.org/10.1016/j.jaci.2022.02.003
Tusheva I, Tusheva I, Boshkovski VB, Bouazzi D, Medianfer CE, Christensen R, et al. Prevalence of hidradenitis suppurativa in Skopje, North Macedonia. Dermatology. 2025;241(Suppl 1):81-6. https://doi.org/10.1159/000539140 PMid:40623381 PMCid:PMC12233977 DOI: https://doi.org/10.1159/000539140
Bouazzi D, Andersen RK, Vinding GR, Medianfar CE, Nielsen SM, Saunte DML, et al. The Global Hidradenitis Suppurativa Atlas methodology: combining global proportions in a pooled analysis. Dermatology. 2024;240(3):369-75. https://doi.org/10.1159/000536389 PMid:38354718 PMCid:PMC12233972 DOI: https://doi.org/10.1159/000536389
Kromann CB, Ibler KS, Kristiansen VB, Jemec GBE. The influence of body weight on the prevalence and severity of hidradenitis suppurativa. Acta Derm Venereol. 2014;94(5):553-7. https://doi.org/10.2340/00015555-1800 PMid:24577555 DOI: https://doi.org/10.2340/00015555-1800
Raufi A, Konstantinova MK. Prevalence of overweight and obesity in children: variation in different ethnicities, age, and sex in North Macedonia. Prilozi. 2022;43(2):23-31. https://doi.org/10.2478/prilozi-2022-0015 PMid:35843913 DOI: https://doi.org/10.2478/prilozi-2022-0015
Ahmeti I, Bitovska I, Markovic S, Sukarova-Angelovska E, Jovanovska-Misevska S, Kocinski G. Growing prevalence and incidence of diabetes in Republic of Macedonia in the past 5 years based on data from the National System for Electronic Health Records. Open Access Maced J Med Sci. 2020;8(B):643-5. https://doi.org/10.3889/oamjms.2020.5071 DOI: https://doi.org/10.3889/oamjms.2020.5071
Swarup S, Ahmed I, Grigorova Y, et al. Metabolic syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.
Gastaldelli A. Measuring and estimating insulin resistance in clinical and research settings. Obesity (Silver Spring). 2022;30(8):1549-63. https://doi.org/10.1002/oby.23503 PMid:35894085 PMCid:PMC9542105 DOI: https://doi.org/10.1002/oby.23503
Madan R, Varghese RT. Assessing insulin sensitivity and resistance in humans. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2024.
Kurniawan LB. Triglyceride-glucose index as a biomarker of insulin resistance, diabetes mellitus, metabolic syndrome, and cardiovascular disease: a review. EJIFCC. 2024;35(1):44-51.
Son DH, Kim W, Lee YH, et al. Comparison of triglyceride-glucose index and HOMA-IR for predicting prevalence and incidence of metabolic syndrome. Nutr Metab Cardiovasc Dis. 2022;32(3):596-604. https://doi.org/10.1016/j.numecd.2021.11.017 PMid:35090800 DOI: https://doi.org/10.1016/j.numecd.2021.11.017
Zeng P, Cai X, Yu X, Huang L, Chen X. HOMA-IR is an effective biomarker of non-alcoholic fatty liver disease in non-diabetic population. J Int Med Res. 2023;51(10):3000605231204462. https://doi.org/10.1177/03000605231204462 PMid:37862786 PMCid:PMC10590044 DOI: https://doi.org/10.1177/03000605231204462
González-Villanueva I, DeGracia C, Planells M, Poveda I, Álvarez P, Schneller-Pavalescu L, et al. Hidradenitis suppurativa is associated with non-alcoholic fatty liver disease: a cross-sectional study. Acta Derm Venereol. 2020;100(15):adv00239. https://doi.org/10.2340/00015555-3597 PMid:32725250 PMCid:PMC9207634 DOI: https://doi.org/10.2340/00015555-3597
Damiani G, Leone S, Fajgenbaum K, et al. Nonalcoholic fatty liver disease prevalence in an Italian cohort of patients with hidradenitis suppurativa: a multicenter retrospective analysis. World J Hepatol. 2019;11(5):391-401. https://doi.org/10.4254/wjh.v11.i4.391 PMid:31114643 PMCid:PMC6504856 DOI: https://doi.org/10.4254/wjh.v11.i4.391
Cartron A, Driscoll MS. Comorbidities of hidradenitis suppurativa: a review of the literature. Int J Womens Dermatol. 2019;5(5):330-4. https://doi.org/10.1016/j.ijwd.2019.06.026 PMid:31909152 PMCid:PMC6938918 DOI: https://doi.org/10.1016/j.ijwd.2019.06.026
Vilanova I, Hernández JL, Mata C, Durán C, García-Unzueta MT, Portilla V, et al. Insulin resistance in hidradenitis suppurativa: a case-control study. J Eur Acad Dermatol Venereol. 2018;32(5):820-4. https://doi.org/10.1111/jdv.14894 PMid:29485215 DOI: https://doi.org/10.1111/jdv.14894
Alba M, Rudd N, Zakaria A, Chang AY, Amerson EH. Hidradenitis suppurativa is associated with cardiometabolic comorbidities in a racially and ethnically diverse safety-net population: a cross-sectional analysis. JAAD Int. 2025;18:131-3. https://doi.org/10.1016/j.jdin.2024.10.003 PMid:39719958 PMCid:PMC11667013 DOI: https://doi.org/10.1016/j.jdin.2024.10.003
Tzellos T, Zouboulis CC, Gulliver W, Cohen AD, Wolkenstein P, Jemec GBE. Cardiovascular disease risk factors in patients with hidradenitis suppurativa: a systematic review and meta-analysis of observational studies. Br J Dermatol. 2015;173(5):1142-55. https://doi.org/10.1111/bjd.14024 PMid:26153913 DOI: https://doi.org/10.1111/bjd.14024
Laplante M, Sabatini DM. mTOR signaling at a glance. J Cell Sci. 2009;122(Pt 20):3589-94. https://doi.org/10.1242/jcs.051011 PMid:19812304 PMCid:PMC2758797 DOI: https://doi.org/10.1242/jcs.051011
Linde-Garelli KY, Rogala KB. Structural mechanisms of the mTOR pathway. Curr Opin Struct Biol. 2023;82:102663. https://doi.org/10.1016/j.sbi.2023.102663 PMid:37572585 DOI: https://doi.org/10.1016/j.sbi.2023.102663
Liu GY, Sabatini DM. mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol. 2020;21(4):183-203. https://doi.org/10.1038/s41580-019-0199-y PMid:31937935 PMCid:PMC7102936 DOI: https://doi.org/10.1038/s41580-019-0199-y
Howell JJ, Hellberg K, Turner M, Talbott G, Kolar MJ, Ross DS, et al. Metformin inhibits hepatic mTORC1 signaling via dose-dependent mechanisms involving AMPK and the TSC complex. Cell Metab. 2017;25(2):463-71. https://doi.org/10.1016/j.cmet.2016.12.009 PMid:28089566 PMCid:PMC5299044 DOI: https://doi.org/10.1016/j.cmet.2016.12.009
Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017;542(7640):177-85. https://doi.org/10.1038/nature21363 PMid:28179656 DOI: https://doi.org/10.1038/nature21363
Alexander S, De Siqueira MK, Seale P, Villanueva CJ. Adipose-tissue plasticity in health and disease. Cell. 2022;185(3):419-46. https://doi.org/10.1016/j.cell.2021.12.016 PMid:35120662 PMCid:PMC11152570 DOI: https://doi.org/10.1016/j.cell.2021.12.016
Mraz M, Haluzik M. The role of adipose tissue immune cells in obesity and low-grade inflammation. J Endocrinol. 2014;222(3):R113-27. https://doi.org/10.1530/JOE-14-0283 PMid:25006217 DOI: https://doi.org/10.1530/JOE-14-0283
Miranda K, Yang X, Bam M, et al. MicroRNA-30 modulates metabolic inflammation by regulating Notch signaling in adipose tissue macrophages. Int J Obes (Lond). 2018;42(6):1140-50. https://doi.org/10.1038/s41366-018-0114-1 PMid:29899524 PMCid:PMC6195825 DOI: https://doi.org/10.1038/s41366-018-0114-1
Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract. 2014;105(2):141-50. https://doi.org/10.1016/j.diabres.2014.04.006 PMid:24798950 PMCid:PMC12126271 DOI: https://doi.org/10.1016/j.diabres.2014.04.006
Malara A, Hughes R, Jennings L, Sweeney CM, Lynch M, Awdeh F, et al. Adipokines are dysregulated in patients with hidradenitis suppurativa. Br J Dermatol. 2018;178(3):792-3. https://doi.org/10.1111/bjd.15904 PMid:28834543 DOI: https://doi.org/10.1111/bjd.15904
González-López MA, Vilanova I, Ocejo-Viñals G, González-Vela C, Val-Bernal JF, Martínez-Taboada VM, et al. Circulating levels of adiponectin, leptin, resistin and visfatin in non-diabetic patients with hidradenitis suppurativa. Arch Dermatol Res. 2020;312(9):595-600. https://doi.org/10.1007/s00403-019-02018-4 PMid:31786710 DOI: https://doi.org/10.1007/s00403-019-02018-4
Mintoff D, Benhadou F, Pace NP, Frew JW. Metabolic syndrome and hidradenitis suppurativa: epidemiological, molecular and therapeutic aspects. Int J Dermatol. 2022;61(2):143-56. https://doi.org/10.1111/ijd.15910 PMid:34530487 DOI: https://doi.org/10.1111/ijd.15910
Barbaresko J, Koch M, Schulze MB, Nöthlings U. Dietary pattern analysis and biomarkers of low-grade inflammation: a systematic literature review. Nutr Rev. 2013;71(8):511-27. https://doi.org/10.1111/nure.12035 PMid:23865797 DOI: https://doi.org/10.1111/nure.12035
Corcoran C, Jacobs TF. Metformin. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025.
Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001;108(8):1167-74. https://doi.org/10.1172/JCI13505 PMid:11602624 PMCid:PMC209533 DOI: https://doi.org/10.1172/JCI13505
Foretz M, Guigas B, Viollet B. Metformin: update on mechanisms of action and repurposing potential. Nat Rev Endocrinol. 2023;19(8):460-76. https://doi.org/10.1038/s41574-023-00833-4 PMid:37130947 PMCid:PMC10153049 DOI: https://doi.org/10.1038/s41574-023-00833-4
Hambly R, Kearney N, Hughes R, Fletcher JM, Kirby B. Metformin treatment of hidradenitis suppurativa: effect on metabolic parameters, inflammation, cardiovascular risk biomarkers, and immune mediators. Int J Mol Sci. 2023;24(8):6969. https://doi.org/10.3390/ijms24086969 PMid:37108132 PMCid:PMC10138328 DOI: https://doi.org/10.3390/ijms24086969
Petrasca A, Hambly R, Kearney N, Smith CM, Pender EK, Mac Mahon J, et al. Metformin has anti-inflammatory effects and induces immunometabolic reprogramming via multiple mechanisms in hidradenitis suppurativa. Br J Dermatol. 2023;189(6):730-40. https://doi.org/10.1093/bjd/ljad305 PMid:37648653 PMCid:PMC13077222 DOI: https://doi.org/10.1093/bjd/ljad305
Melnik BC. Metformin attenuates mechanistic target of rapamycin complex 1/hypoxia-inducible factor-1α-driven glycolysis reducing keratinocyte and T helper 17 cell proliferation in hyperproliferative inflammatory skin diseases. Br J Dermatol. 2023;189(6):652-3. https://doi.org/10.1093/bjd/ljad362 PMid:37932820 DOI: https://doi.org/10.1093/bjd/ljad362
Verdolini R, Clayton N, Smith A, Alwash N, Mannello B. Metformin for the treatment of hidradenitis suppurativa: a little help along the way. J Eur Acad Dermatol Venereol. 2013;27(9):1101-8. https://doi.org/10.1111/j.1468-3083.2012.04668.x PMid:22882365 DOI: https://doi.org/10.1111/j.1468-3083.2012.04668.x
Jennings L, Hambly R, Hughes R, Moriarty B, Kirby B. Metformin use in hidradenitis suppurativa. J Dermatolog Treat. 2020;31(3):261-3. https://doi.org/10.1080/09546634.2019.1592100 PMid:30893570 DOI: https://doi.org/10.1080/09546634.2019.1592100
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2026 ivana Tusheva, Irena Dimitrovska, Vesna Trajkova, Vesna Brishkoska-Boshkovski , Tatjana Ruskovska (Author)

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0)
