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Abstract

Introduction

Obesity is a major risk factor for metabolic and cardiovascular disorders. Recently, emerging biomarkers, such as the Visceral Adiposity Index (VAI) and Lipid Accumulation Product (LAP), have garnered attention for their utility in assessing visceral obesity. Bilirubin, a potent endogenous antioxidant, has been associated with protective effects against various diseases. This study aims to investigate the relationship between serum total bilirubin (STB) levels and VAI/LAP in adults.

Methods

This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2003 and 2020. The calculation of VAI and LAP was performed computationally. Weighted multivariate regression models were used to explore the potential correlation between STB levels and VAI or LAP. RCS curves were used to identify the potential non-linear relationship. Moreover, subgroup analyses were conducted to examine heterogeneity across different populations.

Results

The analysis included a cohort of 10,625 individuals aged 20 to 85 years. Both unadjusted and adjusted statistical models revealed a significant negative association between STB levels and VAI or LAP (all < 0.001). RCS indicates that these relationships are linear. Subgroup analyses identified particularly strong associations in non-smokers aged 20-59 without hypertension/diabetes ( < 0.05).

Discussion

Our study's strengths include the use of nationally representative data with appropriate weighting, comprehensive adjustment for confounding variables, and pioneering research on the link between serum bilirubin levels and visceral fat indices, which may indicate early metabolic risk markers. This finding highlights the significant role of bilirubin in body fat distribution and lipid metabolism.

Conclusion

This study revealed that STB was associated with VAI or LAP among the specific general American population aged 20-59 without hypertension/diabetes. Further prospective investigations are warranted to clarify the temporal relationship between STB and novel obesity indices.

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2025-07-23
2025-09-14

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References

  1. Goossens G.H. The metabolic phenotype in obesity: Fat mass, ody fat distribution, and adipose tissue function. Obes. Facts 2017 10 3 207 215 10.1159/000471488 28564650
    [Google Scholar]
  2. Yucel N. Arany Z. Fat, obesity, and the endothelium. Curr. Opin. Physiol. 2019 12 44 50 10.1016/j.cophys.2019.09.003 31976384
    [Google Scholar]
  3. Mallik R. Carpenter J. Zalin A. Assessment of obesity. Clin. Med. 2023 23 4 299 303 10.7861/clinmed.2023‑0148 37524433
    [Google Scholar]
  4. Chung S.T. Krenek A. Magge S.N. Childhood obesity and cardiovascular disease risk. Curr. Atheroscler. Rep. 2023 25 7 405 415 10.1007/s11883‑023‑01111‑4 37256483
    [Google Scholar]
  5. Rohm T.V. Meier D.T. Olefsky J.M. Donath M.Y. Inflammation in obesity, diabetes, and related disorders. Immunity 2022 55 1 31 55 10.1016/j.immuni.2021.12.013 35021057
    [Google Scholar]
  6. Boutari C. DeMarsilis A. Mantzoros C.S. Obesity and diabetes. Diabetes Res. Clin. Pract. 2023 202 110773 10.1016/j.diabres.2023.110773 37356727
    [Google Scholar]
  7. Kim D.S. Scherer P.E. Obesity, diabetes, and increased cancer progression. Diabetes Metab. J. 2021 45 6 799 812 10.4093/dmj.2021.0077 34847640
    [Google Scholar]
  8. Jiang Z. Wang Y. Zhao X. Obesity and chronic kidney disease. Am. J. Physiol. Endocrinol. Metab. 2023 324 1 E24 E41 10.1152/ajpendo.00179.2022 36383637
    [Google Scholar]
  9. Hojs R. Ekart R. Bevc S. Vodošek Hojs N. Chronic kidney disease and obesity. Nephron J. 2023 147 11 660 664 10.1159/000531379 37271131
    [Google Scholar]
  10. Yau K. Kuah R. Cherney D.Z.I. Lam T.K.T. Obesity and the kidney: Mechanistic links and therapeutic advances. Nat. Rev. Endocrinol. 2024 20 6 321 335 10.1038/s41574‑024‑00951‑7 38351406
    [Google Scholar]
  11. Bastien M. Poirier P. Lemieux I. Després J.P. Overview of epidemiology and contribution of obesity to cardiovascular disease. Prog. Cardiovasc. Dis. 2014 56 4 369 381 10.1016/j.pcad.2013.10.016 24438728
    [Google Scholar]
  12. Fang H. Berg E. Cheng X. Shen W. How to best assess abdominal obesity. Curr. Opin. Clin. Nutr. Metab. Care 2018 21 5 360 365 10.1097/MCO.0000000000000485 29916924
    [Google Scholar]
  13. Silver H.J. Welch B. Avison M.J. Niswender K.D. Imaging body composition in obesity and weight loss: challenges and opportunities. Diabetes Metab. Syndr. Obes. 2010 3 337 347 10.2147/DMSO.S9454 21437103
    [Google Scholar]
  14. Ahn N. Baumeister S.E. Amann U. Visceral adiposity index (VAI), lipid accumulation product (LAP), and product of triglycerides and glucose (TyG) to discriminate prediabetes and diabetes. Sci. Rep. 2019 9 1 9693 10.1038/s41598‑019‑46187‑8 31273286
    [Google Scholar]
  15. Maturana M.A. Moreira R.M.C. Spritzer P.M. Lipid accumulation product (LAP) is related to androgenicity and cardiovascular risk factors in postmenopausal women. Maturitas 2011 70 4 395 399 10.1016/j.maturitas.2011.09.012 22018728
    [Google Scholar]
  16. Costa E.C. Sá J.C. Soares E.M. Lemos T.M. Maranhão T.M. Azevedo G.D. Evaluation of cardiovascular risk by the LAP index in non-obese patients with polycystic ovary syndrome. Arq. Bras. Endocrinol. Metabol 2010 54 7 630 635 10.1590/S0004‑27302010000700007 21085768
    [Google Scholar]
  17. Kalakonda A. Jenkins B.A. John S. Physiology, Bilirubin. In:StatPearls. Treasure Island, FL StatPearls Publishing 2021
    [Google Scholar]
  18. Soto Conti C.P. Bilirubin: The toxic mechanisms of an antioxidant molecule. Arch. Argent. Pediatr. 2021 119 1 e18 e25 10.5546/aap.2021.eng.e18 33458986
    [Google Scholar]
  19. Jansen T. Daiber A. Direct antioxidant properties of bilirubin and biliverdin. Is there a role for biliverdin reductase. Front. Pharmacol. 2012 3 30 10.3389/fphar.2012.00030 22438843
    [Google Scholar]
  20. Stec D.E. John K. Trabbic C.J. Bilirubin binding to PPARα inhibits lipid accumulation. PLoS One 2016 11 4 e0153427 10.1371/journal.pone.0153427 27071062
    [Google Scholar]
  21. Hinds T.D. Adeosun S.O. Alamodi A.A. Stec D.E. Does bilirubin prevent hepatic steatosis through activation of the PPARα nuclear receptor? Med. Hypotheses 2016 95 54 57 10.1016/j.mehy.2016.08.013 27692168
    [Google Scholar]
  22. Creeden J.F. Gordon D.M. Stec D.E. Hinds T.D. Bilirubin as a metabolic hormone: The physiological relevance of low levels. Am. J. Physiol. Endocrinol. Metab. 2021 320 2 E191 E207 10.1152/ajpendo.00405.2020 33284088
    [Google Scholar]
  23. Seyed Khoei N. Wagner K.H. Sedlmeier A.M. Gunter M.J. Murphy N. Freisling H. Bilirubin as an indicator of cardiometabolic health: A cross-sectional analysis in the UK Biobank. Cardiovasc. Diabetol. 2022 21 1 54 10.1186/s12933‑022‑01484‑x 35436955
    [Google Scholar]
  24. Amor A.J. Ortega E. Perea V. Relationship between total serum bilirubin levels and carotid and femoral atherosclerosis in familial dyslipidemia. Arterioscler. Thromb. Vasc. Biol. 2017 37 12 2356 2363 10.1161/ATVBAHA.117.310071 29074587
    [Google Scholar]
  25. Su Q. Chen H. Du S. Du Set al. Association between serum bilirubin, lipid levels, and prevalence of femoral and carotid atherosclerosis: A population-based cross-sectional study. Arterioscler. Thromb. Vasc. Biol. 2023 43 1 136 145 10.1161/ATVBAHA.122.318086 36453272
    [Google Scholar]
  26. Hao H. Guo H. Ma R. Association of total bilirubin and indirect bilirubin content with metabolic syndrome among Kazakhs in Xinjiang. BMC Endocr. Disord. 2020 20 1 110 10.1186/s12902‑020‑00563‑y 32698889
    [Google Scholar]
  27. Kipp Z.A. Martinez G.J. Bates E.A. Bilirubin nanoparticle treatment in obese mice inhibits hepatic ceramide production and remodels liver fat content. Metabolites 2023 13 2 215 10.3390/metabo13020215 36837834
    [Google Scholar]
  28. El-Eshmawy M.M. Mahsoub N. Asar M. Elsehely I. Association between total bilirubin levels and cardio-metabolic risk factors related to obesity. Endocr. Metab. Immune Disord. Drug Targets 2022 22 1 64 70 10.2174/1871530321999210128201259 33511960
    [Google Scholar]
  29. DiNicolantonio J.J. McCarty M.F. O’Keefe J.H. Antioxidant bilirubin works in multiple ways to reduce risk for obesity and its health complications. Open Heart 2018 5 2 e000914 10.1136/openhrt‑2018‑000914 30364545
    [Google Scholar]
  30. Naeini F. Zarezadeh M. Mohiti S. Tutunchi H. Ebrahimi Mamaghani M. Ostadrahimi A. Spirulina supplementation as an adjuvant therapy in enhancement of antioxidant capacity: A systematic review and meta-analysis of controlled clinical trials. Int. J. Clin. Pract. 2021 75 10 e14618 10.1111/ijcp.14618 34235823
    [Google Scholar]
  31. Ziyaei K. Abdi F. Mokhtari M. Daneshmehr M.A. Ataie Z. Phycocyanin as a nature-inspired antidiabetic agent: A systematic review. Phytomedicine 2023 119 154964 10.1016/j.phymed.2023.154964 37544212
    [Google Scholar]
  32. Algren M.H. Bak C.K. Berg-Beckhoff G. Andersen P.T. Health-risk behaviour in deprived neighbourhoods compared with non-deprived neighbourhoods: A systematic literature review of quantitative observational Studies. PLoS One 2015 10 10 e0139297 10.1371/journal.pone.0139297 26506251
    [Google Scholar]
  33. Mao J. Gan S. Zhou Q. Positive correlation between lipid accumulation product index and arterial stiffness in Chinese patients with type 2 diabetes. Front. Endocrinol. 2023 14 1277162 10.3389/fendo.2023.1277162 38075069
    [Google Scholar]
  34. Mazidi M. Kengne A.P. Katsiki N. Mikhailidis D.P. Banach M. Lipid accumulation product and triglycerides/glucose index are useful predictors of insulin resistance. J. Diabetes Complications 2018 32 3 266 270 10.1016/j.jdiacomp.2017.10.007 29395839
    [Google Scholar]
  35. Qin Y. Qiao Y. Wang D. Visceral adiposity index is positively associated with fasting plasma glucose: A cross-sectional study from national health and nutrition examination survey 2017–2020. BMC Public Health 2023 23 1 313 10.1186/s12889‑023‑15231‑8 36774500
    [Google Scholar]
  36. Shao Q. Li J. Wu Y. Enhanced predictive value of lipid accumulation product for identifying metabolic syndrome in the general population of China. Nutrients 2023 15 14 3168 10.3390/nu15143168 37513586
    [Google Scholar]
  37. Zhang Z. Shi D. Zhang Q. Visceral adiposity index (VAI), a powerful predictor of incident hypertension in prehypertensives. Intern. Emerg. Med. 2018 13 4 509 516 10.1007/s11739‑018‑1836‑8 29569088
    [Google Scholar]
  38. Du M.F. Zhang X. Hu G.L. Associations of lipid accumulation product, visceral adiposity index, and triglyceride-glucose index with subclinical organ damage in healthy Chinese adults. Front. Endocrinol. 2023 14 1164592 [PMID: 37795361
    [Google Scholar]
  39. Ebrahimi M. Seyedi S.A. Nabipoorashrafi S.A. Lipid accumulation product (LAP) index for the diagnosis of nonalcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis. Lipids Health Dis. 2023 22 1 41 10.1186/s12944‑023‑01802‑6 36922815
    [Google Scholar]
  40. Cui J. Yang Z. Wang J. A cross-sectional analysis of association between visceral adiposity index and serum anti-aging protein Klotho in adults. Front. Endocrinol. 2023 14 1082504 10.3389/fendo.2023.1082504 36814582
    [Google Scholar]
  41. Zhao K. Wang J. Zhang Y. Sui W. Circulating selenium level was positively related to visceral adiposity index with a non-linear trend: A nationwide study of the general population. Biol. Trace Elem. Res. 2023 [PMID: 37792266
    [Google Scholar]
  42. Yan S. Chen S. Liu Y. Associations of serum carotenoids with visceral adiposity index and lipid accumulation product: A cross-sectional study based on NHANES 2001–2006. Lipids Health Dis. 2023 22 1 209 10.1186/s12944‑023‑01945‑6 38037060
    [Google Scholar]
  43. Huang L. Li Y. Tang R. Bile acids metabolism in the gut-liver axis mediates liver injury during lactation. Life Sci. 2024 338 122380 10.1016/j.lfs.2023.122380 38142738
    [Google Scholar]
  44. Huang C. Xu S. Chen R. Assessing causal associations of bile acids with obesity indicators: A Mendelian randomization study. Medicine 2024 103 25 e38610
    [Google Scholar]
  45. Fu J. Wang Q. Zhang L. Liu J. Wang G. Serum bilirubin level is increased in metabolically healthy obesity. Front. Endocrinol. 2022 12 792795 10.3389/fendo.2021.792795 35432184
    [Google Scholar]
  46. Lanone S. Bloc S. Foresti R. Bilirubin decreases NOS2 expression via inhibition of NAD(P)H oxidase: Implications for protection against endotoxic shock in rats. FASEB J. 2005 19 13 1890 1892 10.1096/fj.04‑2368fje 16129699
    [Google Scholar]
  47. Matsumoto H. Ishikawa K. Itabe H. Maruyama Y. Carbon monoxide and bilirubin from heme oxygenase-1 suppresses reactive oxygen species generation and plasminogen activator inhibitor-1 induction. Mol. Cell. Biochem. 2006 291 1-2 21 28 [PMID: 16625420
    [Google Scholar]
  48. Kim H.J. So H.S. Lee J.H. Heme oxygenase-1 attenuates the cisplatin-induced apoptosis of auditory cells via down-regulation of reactive oxygen species generation. Free Radic. Biol. Med. 2006 40 10 1810 1819 10.1016/j.freeradbiomed.2006.01.018 16678019
    [Google Scholar]
  49. Jiang F. Roberts S.J. Datla S. Dusting G.J. NO modulates NADPH oxidase function via heme oxygenase-1 in human endothelial cells. Hypertension 2006 48 5 950 957 10.1161/01.HYP.0000242336.58387.1f 16982957
    [Google Scholar]
  50. Qin L. Li G. Qian X. Interactive role of the toll-like receptor 4 and reactive oxygen species in LPS-induced microglia activation. Glia 2005 52 1 78 84 10.1002/glia.20225 15920727
    [Google Scholar]
  51. Sorce S. Stocker R. Seredenina T. NADPH oxidases as drug targets and biomarkers in neurodegenerative diseases: What is the evidence? Free Radic. Biol. Med. 2017 112 387 396 10.1016/j.freeradbiomed.2017.08.006 28811143
    [Google Scholar]
  52. André C. Guzman-Quevedo O. Rey C. Inhibiting microglia expansion prevents diet-induced hypothalamic and peripheral inflammation. Diabetes 2017 66 4 908 919 10.2337/db16‑0586 27903745
    [Google Scholar]
  53. Basuroy S. Bhattacharya S. Leffler C.W. Parfenova H. Nox4 NADPH oxidase mediates oxidative stress and apoptosis caused by TNF-α in cerebral vascular endothelial cells. Am. J. Physiol. Cell Physiol. 2009 296 3 C422 C432 10.1152/ajpcell.00381.2008 19118162
    [Google Scholar]
  54. Basuroy S. Tcheranova D. Bhattacharya S. Leffler C.W. Parfenova H. Nox4 NADPH oxidase-derived reactive oxygen species, via endogenous carbon monoxide, promote survival of brain endothelial cells during TNF-α-induced apoptosis. Am. J. Physiol. Cell Physiol. 2011 300 2 C256 C265 10.1152/ajpcell.00272.2010 21123734
    [Google Scholar]
  55. Valdearcos M. Robblee M.M. Benjamin D.I. Nomura D.K. Xu A.W. Koliwad S.K. Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function. Cell Rep. 2014 9 6 2124 2138 10.1016/j.celrep.2014.11.018 25497089
    [Google Scholar]
  56. Liu J. Lai F. Hou Y. Leptin signaling and leptin resistance. Med Rev 2022 2 4 363 384
    [Google Scholar]
  57. Van Doorn C. Macht V.A. Grillo C.A. Reagan L.P. Leptin resistance and hippocampal behavioral deficits. Physiol. Behav. 2017 176 207 213 10.1016/j.physbeh.2017.03.002 28267584
    [Google Scholar]
  58. Picardi P.K. Caricilli A.M. Modulation of hypothalamic PTP 1B in the TNF-α-induced insulin and leptin resistance. FEBS Lett. 2018 592 20 3473 10.1002/1873‑3468.13265 30370663
    [Google Scholar]
  59. Datla S.R. Dusting G.J. Mori T.A. Taylor C.J. Croft K.D. Jiang F. Induction of heme oxygenase-1 in vivo suppresses NADPH oxidase derived oxidative stress. Hypertension 2007 50 4 636 642 10.1161/HYPERTENSIONAHA.107.092296 17679649
    [Google Scholar]
  60. Fujii M. Inoguchi T. Sasaki S. Bilirubin and biliverdin protect rodents against diabetic nephropathy by downregulating NAD(P)H oxidase. Kidney Int. 2010 78 9 905 919 10.1038/ki.2010.265 20686447
    [Google Scholar]
  61. Boland B.S. Dong M.H. Bettencourt R. Barrett-Connor E. Loomba R. Association of serum bilirubin with aging and mortality. J. Clin. Exp. Hepatol. 2014 4 1 1 7 10.1016/j.jceh.2014.01.003 25328328
    [Google Scholar]
  62. Huang S.S. Chan W.L. Leu H.B. Huang P.H. Lin S.J. Chen J.W. Serum bilirubin levels predict future development of metabolic syndrome in healthy middle-aged nonsmoking men. Am. J. Med. 2015 128 10 1138.e35 10.1016/j.amjmed.2015.04.019 25912203
    [Google Scholar]
  63. Carrasquilla G.D. García-Ureña M. Romero-Lado M.J. Kilpeläinen T.O. Estimating causality between smoking and abdominal obesity by Mendelian randomization. Addiction 2024 119 6 1024 1034 10.1111/add.16454 38509034
    [Google Scholar]
  64. Klein S. Gastaldelli A. Yki-Järvinen H. Scherer P.E. Why does obesity cause diabetes? Cell Metab. 2022 34 1 11 20 10.1016/j.cmet.2021.12.012 34986330
    [Google Scholar]
  65. Chandrasekaran P. Weiskirchen R. The role of obesity in type 2 diabetes mellitus-an overview. Int. J. Mol. Sci. 2024 25 3 1882 10.3390/ijms25031882 38339160
    [Google Scholar]
  66. Franco C. Sciatti E. Favero G. Bonomini F. Vizzardi E. Rezzani R. Essential hypertension and oxidative Stress: Novel future perspectives. Int. J. Mol. Sci. 2022 23 22 14489 10.3390/ijms232214489 36430967
    [Google Scholar]
  67. Griendling K.K. Camargo L.L. Rios F.J. Alves-Lopes R. Montezano A.C. Touyz R.M. Oxidative stress and hypertension. Circ. Res. 2021 128 7 993 1020 10.1161/CIRCRESAHA.121.318063 33793335
    [Google Scholar]
  68. Guzik T.J. Touyz R.M. Oxidative stress, inflammation, and vascular aging in hypertension. Hypertension 2017 70 4 660 667 10.1161/HYPERTENSIONAHA.117.07802 28784646
    [Google Scholar]
  69. Mill J.G. Obesity and risk of hypertension: A growing problem in children and adolescents. Arq. Bras. Cardiol. 2023 120 2 e20220940 10.36660/abc.20220940 36888780
    [Google Scholar]
  70. Darenskaya M.A. Kolesnikova L.I. Kolesnikov S.I. Oxidative stress: Pathogenetic role in diabetes mellitus and its complications and therapeutic approaches to correction. Bull. Exp. Biol. Med. 2021 171 2 179 189 10.1007/s10517‑021‑05191‑7 34173093
    [Google Scholar]
  71. Luc K. Schramm-Luc A. Guzik T.J. Mikolajczyk T.P. Oxidative stress and inflammatory markers in prediabetes and diabetes. J. Physiol. Pharmacol. 2019 70 6 10.26402/jpp.2019.6.01 32084643
    [Google Scholar]
  72. Zhang P. Li T. Wu X. Nice E.C. Huang C. Zhang Y. Oxidative stress and diabetes: Antioxidative strategies. Front. Med. 2020 14 5 583 600 10.1007/s11684‑019‑0729‑1 32248333
    [Google Scholar]
  73. Tan Q. Chu H. Wei J. Astaxanthin alleviates hepatic lipid metabolic dysregulation induced by microcystin-LR. Toxins 2024 16 9 401 10.3390/toxins16090401 39330859
    [Google Scholar]
  74. Wang Y. Li H. Fan R. The effects of ferulic acid on the pharmacokinetics of warfarin in rats after biliary drainage. Drug Des. Devel. Ther. 2016 10 2173 2180 10.2147/DDDT.S107917 27462142
    [Google Scholar]
  75. Hu E. Li Z. Li T. A novel microbial and hepatic biotransformation-integrated network pharmacology strategy explores the therapeutic mechanisms of bioactive herbal products in neurological diseases: The effects of Astragaloside IV on intracerebral hemorrhage as an example. Chin. Med. 2023 18 1 40 10.1186/s13020‑023‑00745‑5 37069580
    [Google Scholar]
  76. Zhang L. Virgous C. Si H. Ginseng and obesity: Observations and understanding in cultured cells, animals and humans. J. Nutr. Biochem. 2017 44 1 10 10.1016/j.jnutbio.2016.11.010 27930947
    [Google Scholar]
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A Cross-sectional Data Analysis between Serum Total Bilirubin and Potential Obesity Indices in US Adults
Bentham Science Publishers ; https://doi.org/10.2174/0115665240379393250715115218
/content/journals/cmm/10.2174/0115665240379393250715115218
/content/journals/cmm/10.2174/0115665240379393250715115218
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  • Article Type:     Research Article
Keywords: NAHNES ; visceral adiposity index ; Antioxidants ; Serum total bilirubin ; lipid accumulation product ; Obesity ; Metabolic syndrome

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