Interleukin-6 induces fat loss in cancer cachexia by promoting white adipose tissue lipolysis and browning.

Abstract

BACKGROUND:

Cancer cachexia is a progressive and multi-factorial metabolic syndrome characterized by loss of adipose tissue and skeletal muscle. White adipose tissue (WAT) lipolysis and white-to-brown transdifferentiation of WAT (WAT browning) are proposed to contribute to WAT atrophy in cancer cachexia. Chronic inflammation, mediated by cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), has been reported to promote cancer cachexia. However, whether chronic inflammation promotes cancer cachexia by regulating WAT metabolism and the underlying mechanism remains unclear.

METHODS:

In this study, we first analyzed the association between chronic inflammation and WAT metabolism in gastric and colorectal cancer cachectic patients. In cachectic mice treated with anti-IL-6 receptor antibody, we clarified whether WAT lipolysis and browning were regulated by IL-6.

RESULTS:

Clinical analyses showed positive significant association between serum IL-6 and free fatty acid (FFA) both in early- and late-stage cancer cachexia. However, serum TNF-α was positively associated with serum FFA in the early- but not late-stage cachexia. WAT lipolysis was increased in early- and late-stage cachexia, while WAT browning was detected only in late-stage cachexia. Anti-IL-6 receptor antibody inhibited WAT lipolysis and browning in cachectic mice.

CONCLUSIONS:

Based on these findings, we conclude that chronic inflammation (especially that mediated by IL-6) might promote cancer cachexia by regulating WAT lipolysis in early-stage cachexia and browning in late-stage cachexia.

• Authors: Jun Han, Qingyang Meng, Lei Shen, Guohao Wu
• Journal: Lipids in health and disease (Lipids Health Dis) Vol. 17 Issue 1 Pg. 14 (Jan 16 2018) ISSN: 1476-511X [Electronic] England
• PMID: 29338749 (Publication Type: Journal Article)

Chemical References

• Interleukin-6
• Tumor Necrosis Factor-alpha

Topics

• Adipose Tissue, Brown
• Adipose Tissue, White (metabolism, physiopathology)
• Aged
• Animals
• Cachexia (blood, etiology, metabolism, physiopathology)
• Cell Transdifferentiation
• Colorectal Neoplasms (complications)
• Female
• Humans
• Inflammation (blood, complications, etiology, physiopathology)
• Interleukin-6 (blood, physiology)
• Lipid Mobilization
• Male
• Mice
• Middle Aged
• Neoplasms (complications)
• Stomach Neoplasms (complications)
• Tumor Necrosis Factor-alpha (blood)