In vivo imaging in mice reveals local cell dynamics and inflammation in obese adipose tissue

Abstract

To assess physiological and pathophysiological events that involve dynamic interplay between multiple cell types, real-time, in vivo analysis is necessary. We developed a technique based on confocal laser microscopy that enabled us to analyze and compare the 3-dimensional structures, cellular dynamics, and vascular function within mouse lean and obese adipose tissue in vivo with high spatiotemporal resolution. We found increased leukocyte-EC-platelet interaction in the microcirculation of obese visceral adipose tissue in ob/ob and highfat diet-induced obese mice. These changes were indicative of activation of the leukocyte adhesion cascade, a hallmark of inflammation. Local platelet activation in obese adipose tissue was indicated by increased P-selectin expression and formation of monocyte-platelet conjugates. We observed upregulated expression of adhesion molecules on macrophages and ECs in obese visceral adipose tissue, suggesting that interactions between these cells contribute to local activation of inflammatory processes. Furthermore, administration of anti-ICAM-1 antibody normalized the cell dynamics seen in obese visceral fat. This imaging technique to analyze the complex cellular interplay within obese adipose tissue allowed us to show that visceral adipose tissue obesity is an inflammatory disease. In addition, this technique may prove to be a valuable tool to evaluate potential therapeutic interventions.

Visceral Fat Accumulation is Associated with Oxidative Stress and Increased Matrix Metalloproteinase-9 Expression in Atherogenic Factor-overlapped Model Rats

“…There was also a signi cantly positive relationship between VisF / BW ratio and oxidative stress in all groups, with the underlying pathological conditions of hypertension and hyperlipidemia having a weak yet direct effect on this relationship. Systemic oxidative stress, measured by animals 29,30 . Another proposed cause relates to the abundant synthesis and secretion of angiotensinogen by adipose tissue 31,32 , especially visceral tissue 32,33 .…”

A Western-like fat diet is sufficient to induce a gradual enhancement in fat mass over generations

“…Expression of the P-selectin (Selp) gene, reported to be upregulated in HFD-induced obese mice, increased with generations, suggesting local platelet activation and formation of monocyte-platelet conjugates. These cell-cell interactions could then contribute to local infl ammatory processes ( 25 ). The tendency toward additional proinfl ammatory pathways was also suggested by enhanced expression over generations of neurotensin (Nts), which is known to participate in the activation of the NF-B signaling pathway.…”

Adipose tissue inflammation and ectopic lipid accumulation [Review]

“…This is also the case with adipose tissue inflammation. Recent studies have demonstrated that obese adipose tissue exhibits adipocyte hypertrophy, immune cell infiltration, angiogenesis, and extracellular matrix overproduction during the progression of chronic inflammation [4,5,15,16]. In other words, stromal cells change dramatically in number and cell type during the course of obesity.…”