PMID- 20962049
OWN - NLM
STAT- MEDLINE
DCOM- 20110104
LR  - 20131121
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 151
IP  - 12
DP  - 2010 Dec
TI  - Enhanced amylin-mediated body weight loss in estradiol-deficient diet-induced 
      obese rats.
PG  - 5657-68
LID - 10.1210/en.2010-0590 [doi]
AB  - In rodents, ovariectomy (OVX) elicits weight gain and diminished responsiveness 
      to homeostatic signals. Here we characterized the response of obese OVX rats to 
      peripheral amylin. Rats received sham surgery (SHAM), OVX, or OVX with hormonal 
      replacement (17beta-estradiol, 2 mug per 4 d; OVX+E) and were infused with vehicle or 
      amylin (50 mug/kg . d) for 28 d. Amylin reduced body weight (5.1 +/- 1.1%) and food 
      intake (10.9 +/- 3.4%) in SHAM rats but was twice as efficacious in OVX rats in 
      reducing weight (11.2 +/- 1.9%) and food intake (23.0 +/- 2.0%). There were no 
      differences between amylin-treated SHAM and OVX+E rats. OVX decreased metabolic 
      rate ( approximately 24%) and increased respiratory exchange ratio relative to SHAM. Amylin 
      partially normalized metabolic rate (13% increase) in OVX rats and decreased 
      respiratory exchange ratio in OVX and SHAM rats. Regarding central mechanisms, 
      amylin infusion corrected the OVX-induced decrease in hippocampal neurogenesis 
      and increased immobility in the forced swim test. Additionally, amylin increased 
      neurogenesis ( approximately 2-fold) within the area postrema of OVX rats. To assess the 
      contribution of endogenous leptin to amylin-mediated weight loss in OVX rats, 
      amylin was administered to SHAM or OVX Zucker diabetic fatty rats. In SHAM rats, 
      amylin infusion reduced food intake but not body weight, whereas in OVX Zucker 
      diabetic fatty rats, food intake, body weight, and insulin were reduced. Overall, 
      amylin induced greater body weight loss in the absence of estradiol via central 
      and peripheral actions that did not require leptin. These findings support the 
      clinical investigation of amylin in low estradiol (e.g. postmenopausal) states.
FAU - Trevaskis, James L
AU  - Trevaskis JL
AD  - Amylin Pharmaceuticals, Inc., San Diego, California 92121, USA.
FAU - Turek, Victoria F
AU  - Turek VF
FAU - Wittmer, Carrie
AU  - Wittmer C
FAU - Griffin, Peter S
AU  - Griffin PS
FAU - Wilson, Julie K
AU  - Wilson JK
FAU - Reynolds, James M
AU  - Reynolds JM
FAU - Zhao, Yu
AU  - Zhao Y
FAU - Mack, Christine M
AU  - Mack CM
FAU - Parkes, David G
AU  - Parkes DG
FAU - Roth, Jonathan D
AU  - Roth JD
LA  - eng
PT  - Journal Article
DEP - 20101020
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 0 (Leptin)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Animals
MH  - *Diet
MH  - Eating/drug effects
MH  - Energy Metabolism/drug effects
MH  - Estradiol/*deficiency
MH  - Female
MH  - Islet Amyloid Polypeptide/*pharmacology
MH  - Leptin/metabolism
MH  - Obesity/*metabolism
MH  - Ovariectomy
MH  - Oxygen Consumption/drug effects
MH  - Rats
MH  - Rats, Zucker
MH  - Signal Transduction
MH  - Swimming
MH  - Weight Loss/*drug effects
EDAT- 2010/10/22 06:00
MHDA- 2011/01/05 06:00
CRDT- 2010/10/22 06:00
PHST- 2010/10/22 06:00 [entrez]
PHST- 2010/10/22 06:00 [pubmed]
PHST- 2011/01/05 06:00 [medline]
AID - en.2010-0590 [pii]
AID - 10.1210/en.2010-0590 [doi]
PST - ppublish
SO  - Endocrinology. 2010 Dec;151(12):5657-68. doi: 10.1210/en.2010-0590. Epub 2010 Oct 
      20.