Abstract
BackgroundVisceral adipose tissue foam cells are increased in human obesity, and were implicated in adipose dysfunction and increased cardio-metabolic risk. In the circulation, non-classical monocytes (NCM) are elevated in obesity and associate with atherosclerosis and type 2 diabetes. We hypothesized that circulating NCM correlate and/or are functionally linked to visceral adipose tissue foam cells in obesity, potentially providing an approach to estimate visceral adipose tissue status in the non-surgical obese patient.MethodsWe preformed ex-vivo functional studies utilizing sorted monocyte subclasses from healthy donors. Moreover, we assessed circulating blood monocyte subclasses and visceral fat adipose tissue macrophage (ATM) lipid content by flow-cytometry in paired blood and omental-fat samples collected from patients (n = 65) undergoing elective abdominal surgery.ResultsEx-vivo, NCM and NCM-derived macrophages exhibited lower lipid accumulation capacity compared to classical or intermediate monocytes/-derived macrophages. Moreover, of the three subclasses, NCM exhibited the lowest migration towards adipose tissue conditioned-media. In a cohort of n = 65, increased %NCM associated with higher BMI (r = 0.250,p<0.05) and ATM lipid content (r = 0.303,p<0.05). Among patients with BMI≥25Kg/m2, linear regression models adjusted for age, sex or BMI revealed that NCM independently associate with ATM lipid content, particularly in men.ConclusionsCollectively, although circulating blood NCM are unlikely direct functional precursor cells for adipose tissue foam cells, their increased percentage in the circulation may clinically reflect higher lipid content in visceral ATMs.
Highlights
With the expansion of adipose tissue in obesity, adipose tissue macrophages (ATM) were found to accumulate and support tissue remodeling by storing lipids and scavenging dead adipocyte remains, giving rise to a unique lipid-laden ATM subpopulation–adipose tissue foam cells [1,2,3]
In a cohort of n = 65, increased %non-classical monocytes (NCM) associated with higher body mass index (BMI) (r = 0.250, p
Among patients with BMI25Kg/m2, linear regression models adjusted for age, sex or BMI revealed that NCM independently associate with ATM lipid content, in men
Summary
With the expansion of adipose tissue in obesity, adipose tissue macrophages (ATM) were found to accumulate and support tissue remodeling by storing lipids and scavenging dead adipocyte remains, giving rise to a unique lipid-laden ATM subpopulation–adipose tissue foam cells [1,2,3]. The number of adipose tissue foam cells in omental fat associates with patients’ indicators of insulin resistance and systemic inflammation [3]. Functionally, adipose tissue foam cells isolated from high fat–fed obese mice induce insulin resistance when incubated with adipose tissue explants from lean mice [3]. These data suggest that the presence of lipid-laden ATMs is a feature of obese visceral adipose tissue that contributes to obesity-associated metabolic morbidity. We hypothesized that circulating NCM correlate and/or are functionally linked to visceral adipose tissue foam cells in obesity, potentially providing an approach to estimate visceral adipose tissue status in the non-surgical obese patient
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