Negative legacy of obesity

Kohsuke Shirakawa, Jin Endo, Yoshinori Katsumata, Tsunehisa Yamamoto, Masaharu Kataoka, Sarasa Isobe, Naohiro Yoshida, Keiichi Fukuda, Motoaki Sano

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Obesity promotes excessive inflammation, which is associated with senescence-like changes in visceral adipose tissue (VAT) and the development of type 2 diabetes (T2DM) and cardiovascular diseases. We have reported that a unique population of CD44hi CD62Llo CD4+ T cells that constitutively express PD-1 and CD153 exhibit cellular senescence and cause VAT inflammation by producing large amounts of osteopontin. Weight loss improves glycemic control and reduces cardiovascular disease risk factors, but its long-term effects on cardiovascular events and longevity in obese individuals with T2DM are somewhat disappointing and not well understood. High-fat diet (HFD)-fed obese mice were subjected to weight reduction through a switch to a control diet. They lost body weight and visceral fat mass, reaching the same levels as lean mice fed a control diet. However, the VAT of weight reduction mice exhibited denser infiltration of macrophages, which formed more crown-like structures compared to the VAT of obese mice kept on the HFD. Mechanistically, CD153+ PD-1+ CD4+ T cells are long-lived and not easily eliminated, even after weight reduction. Their continued presence maintains a self-sustaining chronic inflammatory loop via production of large amounts of osteopontin. Thus, we concluded that T-cell senescence is essentially a negative legacy effect of obesity.

Original languageEnglish
Article numbere0186303
JournalPloS one
Volume12
Issue number10
DOIs
Publication statusPublished - 2017 Oct

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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