Physiological Oxygen Levels Differentially Regulate Adipokine Production in Abdominal and Femoral Adipocytes from Individuals with Obesity Versus Normal Weight

Ioannis G Lempesis; Nicole Hoebers; Yvonne Essers; Johan W E Jocken; Kasper M A Rouschop; Ellen E Blaak; Konstantinos N Manolopoulos; Gijs H Goossens

doi:10.3390/cells11223532

Physiological Oxygen Levels Differentially Regulate Adipokine Production in Abdominal and Femoral Adipocytes from Individuals with Obesity Versus Normal Weight

Cells. 2022 Nov 8;11(22):3532. doi: 10.3390/cells11223532.

Authors

Ioannis G Lempesis^{1

2

3}, Nicole Hoebers², Yvonne Essers², Johan W E Jocken², Kasper M A Rouschop⁴, Ellen E Blaak², Konstantinos N Manolopoulos^{1

3}, Gijs H Goossens²

Affiliations

¹ Institute of Metabolism and Systems Research (IMSR), College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
² Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, 6229 ER Maastricht, The Netherlands.
³ Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham B15 2TT, UK.
⁴ Radiotherapy, GROW School for Oncology & Reproduction, Maastricht University Medical Centre+, 6229 ER Maastricht, The Netherlands.

Abstract

Adipose tissue (AT) inflammation may increase obesity-related cardiometabolic complications. Altered AT oxygen partial pressure (pO₂) may impact the adipocyte inflammatory phenotype. Here, we investigated the effects of physiological pO₂ levels on the inflammatory phenotype of abdominal (ABD) and femoral (FEM) adipocytes derived from postmenopausal women with normal weight (NW) or obesity (OB). Biopsies were collected from ABD and FEM subcutaneous AT in eighteen postmenopausal women (aged 50-65 years) with NW (BMI 18-25 kg/m², n = 9) or OB (BMI 30-40 kg/m², n = 9). We compared the effects of prolonged exposure to different physiological pO₂ levels on adipokine expression and secretion in differentiated human multipotent adipose-derived stem cells. Low physiological pO₂ (5% O₂) significantly increased leptin gene expression/secretion in ABD and FEM adipocytes derived from individuals with NW and OB compared with high physiological pO₂ (10% O₂) and standard laboratory conditions (21% O₂). Gene expression/secretion of IL-6, DPP-4, and MCP-1 was reduced in differentiated ABD and FEM adipocytes from individuals with OB but not NW following exposure to low compared with high physiological pO₂ levels. Low physiological pO₂ decreases gene expression and secretion of several proinflammatory factors in ABD and FEM adipocytes derived from individuals with OB but not NW.

Keywords: adipokines; adipose tissue; body fat distribution; hypoxia; inflammation; obesity pathophysiology.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes / metabolism
Adipokines* / metabolism
Adipose Tissue / metabolism
Female
Humans
Obesity / metabolism
Oxygen* / metabolism

Substances

Adipokines
Oxygen

Grants and funding

This work was supported by the European Foundation for the Study of Diabetes (EFSD) under an EFSD/Lilly European Diabetes Research Program grant to Gijs H. Goossens and Konstantinos N. Manolopoulos, and Maastricht University (The Netherlands) and the University of Birmingham (U.K.) under a joint Ph.D. scholarship grant to Gijs H. Goossens and Konstantinos N. Manolopoulos.