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Hypoxia and extra-cellular matrix gene expression in adipose tissue associates with reduced insulin sensitivity in black South African women

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Abstract

Black South African women are more insulin resistant and have increased gluteal subcutaneous adipose tissue hypertrophy than white South African women. We tested the hypothesis that adipose tissue hypoxia and extracellular matrix gene expression in gluteal and abdominal subcutaneous adipose tissue is higher in black than white women, and associates with reduced insulin sensitivity in black women. Insulin sensitivity (frequently sampled intravenous glucose tolerance test), gluteal and abdominal subcutaneous adipose tissue mRNA levels of hypoxia- and extracellular matrix-related genes were measured in normal-weight and obese premenopausal black (n = 30) and white (n = 26) South African women at baseline, and in black women, at 5-year follow-up (n = 10). Compared to obese white women, obese black women had higher expression of hypoxia inducible factor 1, collagen Vα1 and collagen VIα1 and reduced vascular endothelial growth factor-α expression in gluteal (p < 0.05) but not abdominal subcutaneous adipose tissue depots. Independent of age and body fatness, gluteal expression of hypoxia inducible factor 1 (r = −0.55; p = 0.01), collagen Vα1 (r = −0.41; p = 0.05) and collagen VIα1 (r = −0.47; p = 0.03) correlated with reduced insulin sensitivity in black women only. Over a 5-year follow-up, changes in gluteal hypoxia inducible factor 1 (r = 0.77; p = 0.01) collagen Vα1 (r = 0.71; p = 0.02) and collagen VIα1 (r = 0.81; p < 0.01) expression correlated positively with the change in fasting insulin concentrations in black women. Compared to their white counterparts, black women expressed higher levels of genes associated with hypoxia and collagen deposition, and the associations between these genes and insulin sensitivity differed by ethnicity. We thus propose that insulin resistance in black women may be related to higher extracellular matrix and hypoxia gene expression.

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Acknowledgments

This work was funded by the National Research Foundation of South Africa (Grant No: 78824), the South African Medical Research Council and the University of Cape Town. The authors would like to acknowledge excellent clinical and technical assistance from Joel Dave, Phillip Hayes, Hendriena Victor, and Nandipha Sinyanya for subject recruitment and translation.

Authors’ contribution

Liske Kotzé-Hörstmann (Conceptual design, data acquisition, statistical analysis and manuscript preparation); Dheshnie Keswell (Conceptual design, data acquisition and critical manuscript revision) Kevin Adams (data acquisition); Thandi Dlamini (data acquisition); Julia Goedecke (Conceptual design, data acquisition, statistical analysis and critical manuscript revision). All authors reviewed and approved the final version of the manuscript

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Authors and Affiliations

  1. Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, Cape Town, South Africa

    Liske M. Kotzé-Hörstmann, Dheshnie Keswell & Julia H. Goedecke

  2. Department of Plastic Surgery, Department of Surgery, University of Cape Town, Cape Town, South Africa

    Kevin Adams

  3. Division of Diabetes and Endocrinology, Department of Medicine, University of Cape Town, Cape Town, South Africa

    Thandiwe Dlamini

  4. Non-Communicable Disease Research Unit, South African Medical Research Council, Cape Town, South Africa

    Julia H. Goedecke

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  1. Liske M. Kotzé-Hörstmann
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Correspondence to Julia H. Goedecke.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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Kotzé-Hörstmann, L.M., Keswell, D., Adams, K. et al. Hypoxia and extra-cellular matrix gene expression in adipose tissue associates with reduced insulin sensitivity in black South African women. Endocrine 55, 144–152 (2017). https://doi.org/10.1007/s12020-016-1089-0

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