Adipose tissue of obese individuals shows impaired oxygen consumption
MedWire News: Individuals with obesity show an impaired adipose tissue blood flow (ATBF) and oxygen partial pressure (AT-PO2) response to glucose intake relative to lean controls, study results show.
However, obese individuals actually had a higher fasting AT-PO2 than controls, suggesting a lower underlying AT oxygen consumption, a theory supported by the secondary finding of lower mitochondrial gene expression in the AT of obese individuals.
AT dysfunction in obesity contributes to chronic, low-grade inflammation that predisposes to Type 2 diabetes mellitus and cardiovascular disease.
However, the inciting event causing the metabolic and endocrine derangements in AT of obese individuals remains to be established.
"It has been proposed that the expansion of AT mass during the progressive development of obesity may lead to a relative oxygen deficit in certain parts of AT because angiogenesis is insufficient to maintain normoxia in the entire AT depot," Gijs Goossens (Maastricht University Medical Centre, The Netherlands) and colleagues comment in the journal Circulation.
To investigate this, the researchers assessed the impact of acute changes in ATBF on AT-PO2 in lean and obese subjects, using both pharmacologic and physiologic approaches to manipulate ATBF.
They also examined insulin sensitivity, AT gene expression of mitochondrial proteins, and inflammatory markers.
Goossens et al found that local administration of angiotensin II (a vasoconstrictor) in abdominal subcutaneous AT decreased ATBF and AT-PO2, whereas infusion of isoprenaline (a vasodilator) evoked the opposite response.
Ingestion of a glucose drink increased ATBF and AT-PO2 in lean subjects, but this response was almost entirely blunted in obese individuals. Notably, fasting AT-PO2 was actually higher in obese subjects than in lean controls, indicating a state of hyperoxia despite the lower ATBF.
This was accompanied by insulin resistance, lower AT capillarization, lower AT expression of genes encoding proteins involved in mitochondrial biogenesis and function, and higher AT gene expression of macrophage infiltration and inflammatory markers in obese individuals.
Discussing the findings, Goossens et al say they have established ATBF as "an important regulator of AT PO2," but add that the hyperoxia state of AT in obese individuals was unexpected and requires further study.
"Our findings may suggest that targeting AT oxygen tension in obese subjects with impaired glucose tolerance could restore the metabolic and endocrine derangements in AT and subsequently improve insulin sensitivity, thereby reducing the risk of developing obesity-related Type 2 diabetes mellitus and cardiovascular disease," they comment.
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By Andrew Czyzewski