title: Basal mTORC2 activity and expression of its components display diurnal variation in mouse perivascular adipose tissue.
abstract: 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.
authors.affiliation: Research Unit, Department of Internal Medicine, University Hospital Zurich, Switzerland; Center of Competence Multimorbidity and University Research Priority Program "Dynamics of Healthy Aging", University of Zurich, Switzerland.
authors.forename: Katja
authors.initials: K
authors.lastname: Drägert
authors.affiliation: Research Unit, Department of Internal Medicine, University Hospital Zurich, Switzerland; Center of Competence Multimorbidity and University Research Priority Program "Dynamics of Healthy Aging", University of Zurich, Switzerland.
authors.forename: Indranil
authors.initials: I
authors.lastname: Bhattacharya
authors.affiliation: Biozentrum, University of Basel, Switzerland.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Hall
authors.affiliation: Research Unit, Department of Internal Medicine, University Hospital Zurich, Switzerland; Center of Competence Multimorbidity and University Research Priority Program "Dynamics of Healthy Aging", University of Zurich, Switzerland.
authors.forename: Rok
authors.initials: R
authors.lastname: Humar
authors.affiliation: Research Unit, Department of Internal Medicine, University Hospital Zurich, Switzerland; Center of Competence Multimorbidity and University Research Priority Program "Dynamics of Healthy Aging", University of Zurich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland.
authors.forename: Edouard
authors.initials: E
authors.lastname: Battegay
authors.affiliation: Research Unit, Department of Internal Medicine, University Hospital Zurich, Switzerland; Center of Competence Multimorbidity and University Research Priority Program "Dynamics of Healthy Aging", University of Zurich, Switzerland. Electronic address: Elvira.haas@usz.ch.
authors.forename: Elvira
authors.initials: E
authors.lastname: Haas
mesh_terms: D002001:Adipose Tissue, Brown / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology*; D002940:Circadian Rhythm; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007249:Inflammation; D007328:Insulin / Q000378:metabolism; D008297:Male; D000076225:Mechanistic Target of Rapamycin Complex 2; D051379:Mice; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*; D019076:Transgenes; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing
chemical_list: D002352:Carrier Proteins; D007328:Insulin; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes; D052247:Nitric Oxide Synthase Type II; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D058570:TOR Serine-Threonine Kinases; D014409:Tumor Necrosis Factor-alpha; C525637:rictor protein, mouse; C561937:Mapkap1 protein, mouse; D048868:Adaptor Proteins, Signal Transducing; C496317:Nos2 protein, mouse
keywords: Diurnal; PKCalpha; Rictor; mSIN1; mTORC2