Editors' ChoiceObesity

Lym(fat)ics

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Science Translational Medicine  06 Jul 2016:
Vol. 8, Issue 346, pp. 346ec107
DOI: 10.1126/scitranslmed.aag3103

One-third of adults in the United States are obese, and the rates of obesity are continuing to rapidly rise worldwide. Obesity is a risk factor for a variety of disorders, including metabolic syndrome and cancer, which add $200 billion to the U.S. health care budget and are associated with chronic inflammation in the adipose tissue. Although it is clear that obesity causes impaired tissue clearance of macromolecules and spontaneous development of lymphedema, a morbidity characterized by accumulation of interstitial fluid and localized adipose deposition, it is not known whether this is caused by dietary influences or directly attributable to weight gain.

García Nores et al. compared the effects of prolonged high-fat diet on lymphatic function in obesity-prone and obesity-resistant mice. They found that diet alone did not induce lymphatic dysfunction and that this response in obese mice correlated with inflammatory cells and lipids accumulating around lymphatics, as well as alterations in lymphatic endothelial cell gene expression. By studying cultured lymphatic endothelial cells, the authors found that stearic acid, a long-chain fatty acid increased in obese tissues, induces apoptosis and growth inhibition in lymphatic endothelial cells. These effects could be rescued by intracellular modulation of vascular endothelial growth factor receptor-3 signaling through phosphatidylinositol 3,4,5-trisphosphate-tyrosine kinase.

This study suggests that obesity-induced inflammation, and not diet per se, results in pathologic changes in lymphatics because of the injury to lymphatic endothelial cells caused by inflamed adipose tissue. It suggests that ameliorating pathologic signaling caused by higher body weight, previously shown to increase lymphedema risk in patients who undergo lymph node dissection as a part of their cancer treatment, alone or in combination with minimizing weight gain may help preserve lymphatic function and prevent lymphedema.

G. D. García Nores et al., Obesity but not high-fat diet impairs lymphatic function. Int. J. Obes. 10.1038/ijo.2016.96 (2016). [Full Text]

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