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Interleukins 6 and 8 and abdominal fat depots are distinct correlates of lipid moieties in healthy pre- and postmenopausal women

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Abstract

Available data associate lipids concentrations in men with body mass index, anabolic steroids, age, and certain cytokines. Data were less clear in women, especially across the full adult lifespan, and when segmented by premenopausal and postmenopausal status. Subjects: 120 healthy women (60 premenopausal and 60 postmenopausal) in Olmsted County, MN, USA, a stable well studied clinical population. Dependent variables: measurements of 10 h fasting high-density lipoprotein cholesterol, total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Independent variables: testosterone, estrone, estradiol, 5-alpha-dihydrotestosterone, and sex-hormone binding globulin (by mass spectrometry); insulin, glucose, and albumin; abdominal visceral, subcutaneous, and total abdominal fat [abdominal visceral fat, subcutaneous fat, total abdominal fat by computerized tomography scan]; and a panel of cytokines (by enzyme-linked immunosorbent assay). Multivariate forward-selection linear-regression analysis was applied constrained to P < 0.01. Lifetime data: High-density lipoprotein cholesterol was correlated jointly with age (P < 0.0001, positively), abdominal visceral fat (P < 0.0001, negatively), and interleukin-6 (0.0063, negatively), together explaining 28.1 % of its variance (P = 2.3 × 10−8). Total cholesterol was associated positively with multivariate age only (P = 6.9 × 10−4, 9.3 % of variance). Triglycerides correlated weakly with sex-hormone binding globulin (P = 0.0115), and strongly with abdominal visceral fat (P < 0.0001), and interleukin-6 (P = 0.0016) all positively (P = 1.6 × 10−12, 38.9 % of variance). Non high-density lipoprotein cholesterol and low-density lipoprotein cholesterol correlated positively with both total abdominal fat and interleukin-8 (P = 2.0 × 10−5, 16.9 % of variance; and P = 0.0031, 9.4 % of variance, respectively). Premenopausal vs. postmenopausal comparisons identified specific relationships that were stronger in premenopausal than postmenopausal individuals, and vice versa. Age was a stronger correlate of low-density lipoprotein cholesterol; interleukin-6 of triglycerides and high-density lipoprotein; and both sex-hormone binding globulin and total abdominal fat of non high-density lipoprotein cholesterol in premenopausal than postmenopausal women. Conversely, sex-hormone binding globulin, abdominal visceral fat, interleukin-8, adiponectin were stronger correlates of triglycerides; abdominal visceral fat, and testosterone of high-density lipoprotein cholesterol; and age of both non high-density lipoprotein and low-density lipoprotein in postmenopausal than premenopausal women. Our data delineate correlations of total abdominal fat and interleukin-8 (both positively) with non high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in healthy women across the full age range of 21–79 years along with even more specific associations in premenopausal and postmenopausal individuals. Whether some of these outcomes reflect causal relationships would require longitudinal and interventional or genetic studies.

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Abbreviations

AVF:

abdominal visceral fat

BMI:

body mass index

E1 :

estrone

E2 :

estradiol

HDL-C:

high-density lipoprotein cholesterol

IL-6:

interleukin-6

IL-8:

interleukin-8

IRB:

Institutional Review Board

LDL-C:

low-density lipoprotein cholesterol

nonHDL-C:

non high-density lipoprotein cholesterol

SCF:

subcutaneous fat

SHBG:

sex-hormone binding globulin

T:

testosterone

TAF:

total abdominal fat

TC:

total cholesterol

TG:

triglycerides

pre-:

premenopausal

post-:

postmenopausal

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Acknowledgments

We thank Jill Smith for support of manuscript preparation; the Mayo Immunochemical Laboratory for assay assistance; and the Mayo research nursing staff for implementing the protocol.

Author contributions

Conception and design of research: JDV, GGK. Performed experiments: RBD, SAT, OPB, RJS. Analyzed data: JDV. Interpreted results of experiments: JDV, RJS, GGK. Drafted manuscript: JDV. Prepared figures: JDV. Edited and revised manuscript: JDV, GGK. Approved final version of manuscript: JDV, RBD, SAT, OPB, RJS, GGK.

Funding

This study was supported in part by R01 AG029362 and P30 DK050456 (Metabolic Studies Core of the Minnesota Obesity Center) from the National Institutes of Health (Bethesda, MD). The project was supported by UL1 TR000135 from the National Center for Advancing Translational Sciences (NCTS) and 60NANB10D005Z from the National Institute of Standards and Technology. Contents are solely the responsibility of the authors and do not necessarily represent the official views of any federal institution.

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Authors and Affiliations

  1. Endocrine Research Unit, Mayo School of Graduate Medical Education, 200 First Street SW, Rochester, MN, 55905, USA

    Johannes D. Veldhuis

  2. Immunochemical Laboratory, 200 First Street SW, Rochester, MN, 55905, USA

    Roy B. Dyer, Sergey A. Trushin & Olga P. Bondar

  3. Department of Neurology, 200 First Street SW, Rochester, MN, 55905, USA

    Sergey A. Trushin

  4. Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Ravinder J. Singh & George G. Klee

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  1. Johannes D. Veldhuis
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Correspondence to Johannes D. Veldhuis.

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Author Contributions

Conception and design of research: JDV, GGK; Performed experiments: RBD, SAT, OPB, RJS; Analyzed data: JDV; Interpreted results of experiments: JDV, RJS, GGK; Drafted manuscript: JDV; Prepared figures: JDV; Edited and revised manuscript: JDV, GGK; Approved final version of manuscript: JDV, RBD, SAT, OPB, RJS, GGK.

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Veldhuis, J.D., Dyer, R.B., Trushin, S.A. et al. Interleukins 6 and 8 and abdominal fat depots are distinct correlates of lipid moieties in healthy pre- and postmenopausal women. Endocrine 54, 671–680 (2016). https://doi.org/10.1007/s12020-016-1041-3

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