Circulating Blood Monocyte Subclasses and Lipid-Laden Adipose Tissue Macrophages in Human Obesity

PLoS One. 2016 Jul 21;11(7):e0159350. doi: 10.1371/journal.pone.0159350. eCollection 2016.

Abstract

Background: Visceral 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.

Methods: We 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.

Results: Ex-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.

Conclusions: Collectively, 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.

MeSH terms

  • Adipose Tissue / pathology*
  • Adult
  • Cell Movement / drug effects
  • Cohort Studies
  • Culture Media, Conditioned / pharmacology
  • Flow Cytometry
  • Humans
  • Lipids / chemistry*
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Male
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • Obesity / blood*
  • Obesity / pathology*
  • Omentum / drug effects
  • Omentum / metabolism

Substances

  • Culture Media, Conditioned
  • Lipids

Grant support

This study was supported by grants from the Ministry of Science, Technology & Space, Israel, & The Ministe're de L'Education National, de I'Enseignement Sup'erieur et de la Recherche, France, and the Deutsche Forschungsgemeinschaft (DFG): SFB 1052/1: ‘Obesity mechanisms’ (project B2). Tal Pecht was supported by a student grant from the National Institute of Biotechnology in the Negev, Ben-Gurion University, Beer-Sheva, Israel. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.