Body fat distribution and obesity: a comparison of upper and lower body adipose tissue biology in humans

Lempesis, Ioannis (2023). Body fat distribution and obesity: a comparison of upper and lower body adipose tissue biology in humans. University of Birmingham. Ph.D.

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Abstract

Obesity is a chronic disease that is linked to increased cardiometabolic disease risk, partially attributable to upper body fat accumulation and adipose tissue (AT) dysfunction. AT dysfunction is characterised by impaired adipokine expression/ secretion, chronic low-grade inflammation, decreased AT blood flow (ATBF), mitochondrial dysfunction, and altered oxygen partial pressure. This thesis investigated the biology of upper and lower body AT in humans with normal weight or obesity, focusing on potential differences in ATBF, the inflammatory phenotype and the oxidative machinery between abdominal and femoral subcutaneous AT. Furthermore, the impact of exposure to various oxygen levels on the inflammatory phenotype of abdominal and femoral adipocytes was examined. First, we discussed the possible role of AT oxygen partial pressure (pO2) in the metabolic and inflammatory perturbations associated with obesity. Next, we determined the feasibility to measure abdominal and femoral ATBF with intravascular percutaneous Doppler ultrasound in humans and performed a series of studies to investigate the inflammatory and oxidative phenotypes of abdominal and femoral subcutaneous AT in postmenopausal women with normal weight or obesity. We found that upper and lower body AT and adipocytes have distinct inflammatory signatures. Furthermore, in vivo AT oxygen fractional extraction and adipocyte oxygen consumption rates were lower in abdominal compared to femoral AT and adipocytes in postmenopausal women. Although lower in obesity, no significant depot-differences in oxidative phosphorylation (OXPHOS) protein expression and mitochondrial (mt)DNA content were apparent. Finally, we investigated the impact of prolonged exposure (14 days) to various pO2 levels on adipokine expression and secretion in differentiated adipose tissue-derived mesenchymal stem cells, demonstrating that low physiological pO2 (5%) decreased gene expression and secretion of several pro-inflammatory factors in both abdominal and femoral adipocytes derived from individuals with obesity but not normal weight. Overall, this thesis provides important insights into the differences between upper and lower body AT biology and the impact of oxygenation on the inflammatory phenotype of human adipocytes.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):

Supervisor(s)	Email	ORCID
Manolopoulos, Konstantinos	UNSPECIFIED	UNSPECIFIED
Lavery, Gareth	UNSPECIFIED	UNSPECIFIED
Blaak, Ellen E.	UNSPECIFIED	UNSPECIFIED
Goossens, Gijs H.	UNSPECIFIED	UNSPECIFIED