PMID- 24010023
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240109
IS  - 2168-8761 (Print)
IS  - 2168-877X (Electronic)
VI  - 1
IP  - 2
DP  - 2013 Jun
TI  - Rapamycin Modulates Markers of Mitochondrial Biogenesis and Fatty Acid Oxidation 
      in the Adipose Tissue of db/db Mice.
PG  - 114-123
AB  - Excess nutrient uptake leads to obesity, insulin resistance, and type 2 diabetes. 
      Mammalian target of the rapamycin (mTOR), a major component of the 
      nutrient-sensing pathway also regulates mitochondrial oxidative function. 
      Rapamycin, a pharmacological inhibitor of mTOR, causes glucose intolerance and 
      inhibits mitochondrial oxidative function. While a number of studies have focused 
      on the effect of rapamycin on control wild-type mice, ours is the first to study 
      the effect of rapamycin on mitochondrial gene expression and insulin sensitivity 
      in the db/db mouse, a model of diabetic dyslipidemia. Female db/+ and db/db mice 
      were fed ad libitum a rapamycin-containing diet or a control diet for 6 months, 
      starting at two months of age. Body weight, fat mass, lean mass and food intake 
      were measured monthly. Effect of rapamycin or control diet on markers of 
      adipogenesis, fatty acid oxidation and mitochondrial biogenesis in the gonadal 
      white adipose tissue (WAT) as well as different serum parameters were assessed. 
      Whole body insulin sensitivity was measured by insulin tolerance test. Rapamycin 
      feeding to db/db mice decreased body weight (58%) and fat mass (33%), elevated 
      markers of fatty acid oxidation and mitochondrial biogenesis in WAT, reduced 
      circulating non-esterified free fatty acids (NEFA), elevated circulating 
      adiponectin and improved insulin sensitivity, compared to control diet fed db/db 
      mice. These data demonstrate that rapamycin exhibits an anti-obesity effect and 
      improves whole body insulin sensitivity in db/db mice and suggest an unexpected 
      effect of simultaneous inhibition mTOR and leptin signaling in mice.
FAU - Deepa, Sathyaseelan S
AU  - Deepa SS
AD  - Barshop Institute for Longevity and Aging Studies, University of Texas Health 
      Science Center at San Antonio, San Antonio, Texas 78245, USA ; Department of 
      Cellular and Structural Biology, University of Texas Health Science Center at San 
      Antonio, San Antonio, Texas 78229, USA.
FAU - Walsh, Michael E
AU  - Walsh ME
AD  - Barshop Institute for Longevity and Aging Studies, University of Texas Health 
      Science Center at San Antonio, San Antonio, Texas 78245, USA ; Department of 
      Cellular and Structural Biology, University of Texas Health Science Center at San 
      Antonio, San Antonio, Texas 78229, USA.
FAU - Hamilton, Ryan T
AU  - Hamilton RT
AD  - Barshop Institute for Longevity and Aging Studies, University of Texas Health 
      Science Center at San Antonio, San Antonio, Texas 78245, USA.
FAU - Pulliam, Daniel
AU  - Pulliam D
AD  - Barshop Institute for Longevity and Aging Studies, University of Texas Health 
      Science Center at San Antonio, San Antonio, Texas 78245, USA ; Department of 
      Cellular and Structural Biology, University of Texas Health Science Center at San 
      Antonio, San Antonio, Texas 78229, USA.
FAU - Shi, Yun
AU  - Shi Y
AD  - Barshop Institute for Longevity and Aging Studies, University of Texas Health 
      Science Center at San Antonio, San Antonio, Texas 78245, USA.
FAU - Hill, Shauna
AU  - Hill S
AD  - Barshop Institute for Longevity and Aging Studies, University of Texas Health 
      Science Center at San Antonio, San Antonio, Texas 78245, USA.
FAU - Li, Yan
AU  - Li Y
AD  - Barshop Institute for Longevity and Aging Studies, University of Texas Health 
      Science Center at San Antonio, San Antonio, Texas 78245, USA.
FAU - Van Remmen, Holly
AU  - Van Remmen H
AD  - Barshop Institute for Longevity and Aging Studies, University of Texas Health 
      Science Center at San Antonio, San Antonio, Texas 78245, USA ; Department of 
      Cellular and Structural Biology, University of Texas Health Science Center at San 
      Antonio, San Antonio, Texas 78229, USA ; Geriatric Research, Education, and 
      Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas 
      78229, USA.
LA  - eng
GR  - I01 BX000517/BX/BLRD VA/United States
GR  - RC2 AG036613/AG/NIA NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - J Biochem Pharmacol Res
JT  - Journal of biochemical and pharmacological research
JID - 101604121
PMC - PMC3760510
MID - NIHMS505765
OTO - NOTNLM
OT  - db/db mouse
OT  - fat oxidation
OT  - insulin sensitivity
OT  - mitochondria
OT  - obesity
EDAT- 2013/09/07 06:00
MHDA- 2013/09/07 06:01
PMCR- 2013/09/03
CRDT- 2013/09/07 06:00
PHST- 2013/09/07 06:00 [entrez]
PHST- 2013/09/07 06:00 [pubmed]
PHST- 2013/09/07 06:01 [medline]
PHST- 2013/09/03 00:00 [pmc-release]
PST - ppublish
SO  - J Biochem Pharmacol Res. 2013 Jun;1(2):114-123.