PMID- 17901224
OWN - NLM
STAT- MEDLINE
DCOM- 20080617
LR  - 20150306
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 148
IP  - 12
DP  - 2007 Dec
TI  - Obesity-induced inflammation in white adipose tissue is attenuated by loss of 
      melanocortin-3 receptor signaling.
PG  - 6186-94
AB  - Metabolic syndrome, a complex of highly debilitating disorders that includes 
      insulin resistance, hypertension, and dyslipidemia, is associated with the 
      development of obesity in humans as well as rodent models. White adipose tissue 
      (WAT) inflammation, caused in part by macrophage infiltration, and fat 
      accumulation in the liver are both linked to development of the metabolic 
      syndrome. Despite large increases in body fat, melanocortin 3-receptor 
      (MC3-R)-deficient mice do not get fatty liver disease or severe insulin 
      resistance. This is in contrast to obese melanocortin 4-receptor 
      (MC4-R)-deficient mice and diet-induced obese (DIO) mice, which show increased 
      adiposity, fatty liver disease, and insulin resistance. We hypothesized that 
      defects in the inflammatory response to obesity may underlie the protection from 
      metabolic syndrome seen in MC3-R null mice. MC4-R mice fed a chow diet show 
      increased proinflammatory gene expression and macrophage infiltration in WAT, as 
      do wild-type (WT) DIO mice. In contrast, MC3-R-deficient mice fed a normal chow 
      diet show neither of these inflammatory changes, despite their elevated adiposity 
      and a comparable degree of adipocyte hypertrophy to the MC4-R null and DIO mice. 
      Furthermore, even when challenged with high-fat chow for 4 wk, a period of time 
      shown to induce an inflammatory response in WAT of WT animals, MC3-R nulls showed 
      an attenuated up-regulation in both monocyte chemoattractant protein-1 (MCP-1) 
      and TNFalpha mRNA in WAT compared with WT high-fat-fed animals.
FAU - Ellacott, Kate L J
AU  - Ellacott KL
AD  - Center for the Study of Weight Regulation and Associated Disorders (L481), Oregon 
      Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 
      97239-3098, USA.
FAU - Murphy, Jonathan G
AU  - Murphy JG
FAU - Marks, Daniel L
AU  - Marks DL
FAU - Cone, Roger D
AU  - Cone RD
LA  - eng
GR  - R01 DK 070332/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 - 20070927
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Dietary Fats)
RN  - 0 (Leptin)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Melanocortin, Type 3)
RN  - 0 (Triglycerides)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adipose Tissue, White/*metabolism/pathology
MH  - Adiposity/drug effects/genetics
MH  - Animals
MH  - Chemokine CCL2/genetics
MH  - Dietary Fats
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Immunohistochemistry
MH  - Inflammation/etiology/genetics/*metabolism
MH  - Insulin Resistance
MH  - Leptin/blood
MH  - Liver/drug effects/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Obesity/blood/chemically induced/*complications
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptor, Melanocortin, Type 3/genetics/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/genetics/*physiology
MH  - Triglycerides/metabolism
MH  - Tumor Necrosis Factor-alpha/genetics
EDAT- 2007/09/29 09:00
MHDA- 2008/06/18 09:00
CRDT- 2007/09/29 09:00
PHST- 2007/09/29 09:00 [pubmed]
PHST- 2008/06/18 09:00 [medline]
PHST- 2007/09/29 09:00 [entrez]
AID - en.2007-0699 [pii]
AID - 10.1210/en.2007-0699 [doi]
PST - ppublish
SO  - Endocrinology. 2007 Dec;148(12):6186-94. doi: 10.1210/en.2007-0699. Epub 2007 Sep 
      27.