PMID- 25475828
OWN - NLM
STAT- MEDLINE
DCOM- 20150924
LR  - 20181113
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Print)
IS  - 1462-8902 (Linking)
VI  - 17
IP  - 3
DP  - 2015 Mar
TI  - Liraglutide, leptin and their combined effects on feeding: additive intake 
      reduction through common intracellular signalling mechanisms.
PG  - 285-93
LID - 10.1111/dom.12423 [doi]
AB  - AIM: To investigate the behavioural and intracellular mechanisms by which the 
      glucagon like peptide-1 (GLP-1) receptor agonist, liraglutide, and leptin in 
      combination enhance the food intake inhibitory and weight loss effects of either 
      treatment alone. METHODS: We examined the effects of liraglutide (a long-acting 
      GLP-1 analogue) and leptin co-treatment, delivered in low or moderate doses 
      subcutaneously (s.c.) or to the third ventricle, respectively, on cumulative 
      intake, meal patterns and hypothalamic expression of intracellular signalling 
      proteins [phosphorylated signal transducer and activator of transcription-3 
      (pSTAT3) and protein tyrosine phosphatase-1B (PTP1B)] in lean rats. RESULTS: A 
      low-dose combination of liraglutide (25 microg/kg) and leptin (0.75 microg) additively 
      reduced cumulative food intake and body weight, a result mediated predominantly 
      through a significant reduction in meal frequency that was not present with 
      either drug alone. Liraglutide treatment alone also reduced meal size; an effect 
      not enhanced with leptin co-administration. Moderate doses of liraglutide 
      (75 microg/kg) and leptin (4 microg), examined separately, each reduced meal frequency, 
      cumulative food intake and body weight; only liraglutide reduced meal size. In 
      combination these doses did not further enhance the anorexigenic effects of 
      either treatment alone. Ex vivo immunoblot analysis showed elevated pSTAT3 in the 
      hypothalamic tissue after liraglutide-leptin co-treatment, an effect which was 
      greater than that of leptin treatment alone. In addition, s.c. liraglutide 
      reduced the expression of PTP1B (a negative regulator of leptin receptor 
      signalling), revealing a potential mechanism for the enhanced pSTAT3 response 
      after liraglutide-leptin co-administration. CONCLUSIONS: Collectively, these 
      results show novel behavioural and molecular mechanisms underlying the additive 
      reduction in food intake and body weight after liraglutide-leptin combination 
      treatment.
CI  - (c) 2014 John Wiley & Sons Ltd.
FAU - Kanoski, S E
AU  - Kanoski SE
AD  - Department of Biological Sciences, University of Southern California, Los 
      Angeles, CA, USA.
FAU - Ong, Z Y
AU  - Ong ZY
FAU - Fortin, S M
AU  - Fortin SM
FAU - Schlessinger, E S
AU  - Schlessinger ES
FAU - Grill, H J
AU  - Grill HJ
LA  - eng
GR  - DK21397/DK/NIDDK NIH HHS/United States
GR  - R56 DK021397/DK/NIDDK NIH HHS/United States
GR  - DK102478/DK/NIDDK NIH HHS/United States
GR  - DK097147/DK/NIDDK NIH HHS/United States
GR  - K01 DK097147/DK/NIDDK NIH HHS/United States
GR  - R01 DK021397/DK/NIDDK NIH HHS/United States
GR  - R03 DK102478/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150108
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Appetite Depressants)
RN  - 0 (Incretins)
RN  - 0 (Leptin)
RN  - 0 (STAT3 Transcription Factor)
RN  - 839I73S42A (Liraglutide)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
SB  - IM
MH  - Animals
MH  - Appetite Depressants/*pharmacology
MH  - Body Weight/drug effects
MH  - Drug Therapy, Combination/methods
MH  - Eating/*drug effects
MH  - Glucagon-Like Peptide 1/*analogs & derivatives/pharmacology
MH  - Hypothalamus/drug effects
MH  - Incretins/*pharmacology
MH  - Leptin/*pharmacology
MH  - Liraglutide
MH  - Male
MH  - Obesity/drug therapy
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 1/*drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - STAT3 Transcription Factor/*drug effects
MH  - *Weight Loss
PMC - PMC4320650
MID - NIHMS646727
OTO - NOTNLM
OT  - GLP-1
OT  - exendin-4
OT  - obesity
OT  - rat
OT  - synergy
OT  - weight loss
COIS- Conflict of interest details: S.E.K., Z.Y.O., and H.J.G. did the conception and 
      design of the research; S.E.K., Z.Y.O., S.M.F., E.S. performed the experiments; 
      S.E.K., Z.Y.O., S.M.F., and E.S.S. analyzed the data; S.E.K., Z.Y.O., S.M.F., 
      E.S.S., and H.J.G. interpreted the results of the experiments; S.E.K. prepared 
      the figures; S.E.K., and Z.Y.O drafted the manuscript; S.E.K., Z.Y.O., S.M.F., 
      E.S.S., and H.J.G. edited and revised the manuscript; S.E.K., Z.Y.O., S.M.F., 
      E.S.S., and H.J.G. approved the final version of the manuscript.
EDAT- 2014/12/06 06:00
MHDA- 2015/09/25 06:00
PMCR- 2016/03/01
CRDT- 2014/12/06 06:00
PHST- 2014/10/08 00:00 [received]
PHST- 2014/11/14 00:00 [revised]
PHST- 2014/12/01 00:00 [accepted]
PHST- 2014/12/06 06:00 [entrez]
PHST- 2014/12/06 06:00 [pubmed]
PHST- 2015/09/25 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - 10.1111/dom.12423 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2015 Mar;17(3):285-93. doi: 10.1111/dom.12423. Epub 2015 Jan 
      8.