Lymphatic Function Regulates Contact Hypersensitivity Dermatitis in Obesity

The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity

“…Further support for a cross-talk between lymphatics and obesity was provided by data showing that obese mice also have impaired lymphatic function, characterized by leaky capillary lymphatics and decreased collecting vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, and decreased expression of lymphatic specific markers compared with lean mice (Garcia Nores et al, 2016; Hespe et al, 2016; Nitti et al, 2016; Savetsky et al, 2015a; Torrisi et al, 2016). Savetsky et al .…”

“…Recent studies suggested that obesity-induced lymphatic dysfunction can intensify the pathological effects of obesity in other organ systems by regulating leukocyte infiltration and expression of inflammatory cytokines (Savetsky et al, 2015a); therefore, obesity-related lymphatic dysfunction worsen the pathological changes associated to obesity. For example, reduced lymphatic function in obese mice favors inflammatory responses in dermatitis, while improving lymphatic function by the injection of recombinant vascular endothelial growth factor-C (VEGF-C), a growth factor that plays a key role in lymphangiogenesis and lymphatic development (Gomez-Ambrosi et al, 2010; Silha et al, 2005; Wada et al, 2011), resulted in considerably decreased dermatitis responses (Savetsky et al, 2015a). These results are also supported by recent studies demonstrating that inhibition of inflammation improves lymphatic function in HFD-induced obesity (Torrisi et al, 2016).…”

Hyperplasia, de novo lymphangiogenesis, and lymphatic regression in mice with tissue-specific, inducible overexpression of murine VEGF-D

“…VEGFR-3 signaling may not only induce hyperplasia, but also impact lymphatic vessel fluid and cell transport in a host of tissue systems (8,14,15,41,42). The Adipo-VD mouse did not display systemic edema, assessed by total body fluid accumulation.…”

Obesity, But Not High Fat Diet, Impairs Lymphatic Function

“…[3][4][5][6][7][8][9][10] However, it remains unclear whether the observed effects on lymphatic function were secondary to weight gain, prolonged exposure to HFD or toxic metabolic by-products of adipose tissue. To address this question, we compared lymphatic function in obesity-prone and obesityresistant mice after prolonged exposure to HFD.…”

“…For example, our group and others have shown that high-fat diet (HFD)-induced obesity markedly decreases interstitial fluid transport, immune cell trafficking and lymphatic collecting vessel pumping. [8][9][10] These negative consequences were correlated with increasing body mass, suggesting that adipose deposition has a role in this response. In contrast, others have reported that high fructose diet-induced metabolic syndrome 11 or hypercholesterolemia 12 decreases collecting vessel pumping and results in lymphatic system abnormalities independent of obesity.…”