Basal mTORC2 activity and expression of its components display diurnal variation in mouse perivascular adipose tissue

Biochem Biophys Res Commun. 2016 Apr 22;473(1):317-322. doi: 10.1016/j.bbrc.2016.03.102. Epub 2016 Mar 22.


In adipose tissue mTOR complex 2 (mTORC2) contributes to the regulation of glucose/lipid metabolism and inflammatory molecule expression. Both processes display diurnal variations during the course of the day. RICTOR and mSIN1 are unique and essential components of mTORC2, which is activated by growth factors including insulin. To assess whether mTORC2 components display diurnal variations, we analyzed steady state mRNA expression levels of Rictor, mSin1, and mTor in various adipose tissues during a 24 h period. Diurnally regulated expression of Rictor was detected in brown adipose tissues displaying highest mRNA expression levels at the beginning of the 12 h light period (zeitgeber time 2, ZT2). Gene expression patterns of mSin1 and mTor displayed a similar diurnal regulation as Rictor in PVAT while smaller changes were detected for these genes in aorta during the course of the day. Basal mTORC2 activity was measured by phosphorylation of protein kinase C (PKC) α at serine 657 was higher at ZT14 as compared with ZT2 in PVAT. In line, gene expression of inflammatory molecules nitric oxide synthase 2 and tumor necrosis factor α was lower at ZT 14 compared to ZT2. Our findings provide evidence for a diurnal regulation of expression of mTORC2 components and activity. Hence, mTORC2 is possibly an integral part of diurnally regulated signaling pathways in PVAT and possibly in other adipose tissues.

Keywords: Diurnal; PKCalpha; Rictor; mSIN1; mTORC2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / physiology*
  • Animals
  • Aorta / metabolism
  • Carrier Proteins / physiology*
  • Circadian Rhythm
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Inflammation
  • Insulin / metabolism
  • Male
  • Mechanistic Target of Rapamycin Complex 2
  • Mice
  • Mice, Inbred C57BL
  • Multiprotein Complexes / physiology*
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphorylation
  • Rapamycin-Insensitive Companion of mTOR Protein
  • TOR Serine-Threonine Kinases / physiology*
  • Transgenes
  • Tumor Necrosis Factor-alpha / metabolism


  • Carrier Proteins
  • Insulin
  • Multiprotein Complexes
  • Rapamycin-Insensitive Companion of mTOR Protein
  • Tumor Necrosis Factor-alpha
  • rictor protein, mouse
  • stress-activated protein kinase-interacting protein, mouse
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Mechanistic Target of Rapamycin Complex 2
  • TOR Serine-Threonine Kinases