High-fat diet induced obesity and age influence the telomere shelterin complex and telomerase gene expression in mouse adipose tissue

Physiol Rep. 2020 Jun;8(11):e14461. doi: 10.14814/phy2.14461.

Abstract

Obesity and aging are linked to inflammation and increased risk of chronic disease. Telomeres are the endcaps of chromosomes that are regulated by telomerase, the enzyme that elongates telomeres, as well as a protein complex known as shelterin. Telomere dysfunction is associated with inflammation, aging, and disease. However, the effect of high-fat diet (HFD) induced obesity and advancing age on the shelterin complex and telomerase in adipose tissue is unknown. The present study investigated the effects of obesity and aging on C57BL/6J mice adipose tissue mRNA expression of shelterin complex genes. Young (YG) mice (3 mo) were randomly assigned to be fed either a high-fat diet (YG + HFD; 60% kcal from fat) or a low-fat diet (YG + LFD; 10% kcal from fat). A subset of mice were aged until 16 months. Body weight and epididymal white adipose tissue (EWAT) weight increased with age or a HFD. There was a trend for increased Terf2 expression, as expression was increased in HFD + YG by ~47% and aged mice by ~80%. Pot1b expression was increased in aged mice by ~35%-60% compared to YG, independent of diet. mTert, the gene that codes for the catalytic subunit of telomerase, was significantly elevated in aged mice. Changes in telomere associated gene expression was accompanied by changes in expression of inflammatory markers Mcp1 and Tnfα. These findings suggest obesity and age impact expression of shelterin complex and telomerase related genes in adipose, perhaps altering telomere function in adipose tissue thereby increasing inflammation and risk of chronic disease.

Keywords: aging; obesity; telomeres.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue / metabolism*
  • Age Factors
  • Animals
  • Cellular Senescence
  • DNA-Binding Proteins / genetics
  • Diet, High-Fat*
  • Gene Expression*
  • Inflammation / genetics
  • Male
  • Mice, Inbred C57BL
  • Obesity / etiology
  • Obesity / genetics*
  • RNA, Messenger
  • Telomerase / genetics*
  • Telomere / metabolism*
  • Telomeric Repeat Binding Protein 2 / genetics*

Substances

  • DNA-Binding Proteins
  • POT1b protein, mouse
  • RNA, Messenger
  • TRF2 protein, mouse
  • Telomeric Repeat Binding Protein 2
  • Telomerase