PMID- 27879248
OWN - NLM
STAT- MEDLINE
DCOM- 20170620
LR  - 20231213
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 312
IP  - 1
DP  - 2017 Jan 1
TI  - High-fat diet-induced obesity regulates MMP3 to modulate depot- and sex-dependent 
      adipose expansion in C57BL/6J mice.
PG  - E58-E71
LID - 10.1152/ajpendo.00128.2016 [doi]
AB  - Increased adipocyte size is hypothesized to signal the recruitment of adipose 
      progenitor cells (APCs) to expand tissue storage capacity. To investigate depot 
      and sex differences in adipose growth, male and female C57BL/6J mice (10 wk-old) 
      were challenged with high-fat (HF) or low-fat (LF) diets (D) for 14 wk. The HFD 
      increased gonadal (GON) depot weight by adipocyte hypertrophy and hyperplasia in 
      females but hypertrophy alone in males. In both sexes, inguinal (ING) adipocytes 
      were smaller than GON, and depot expansion was due to hypertrophy. Matrix 
      metalloproteinase 3 (Mmp3), an antiadipogenic factor, and its inhibitor Timps 
      modulate the extracellular matrix remodeling needed for depot expansion. Mmp3 
      mRNA was depot different (ING > GON), higher in females than males and mainly 
      expressed in APCs. In males, HFD-induced obesity increased tissue and APC Mmp3 
      mRNA levels and MMP3 protein and enzymatic activity. In females however, HFD 
      significantly decreased MMP3 protein without affecting its mRNA levels. MMP3 
      activity also decreased (significant in ING). Timp4 mRNA was expressed mainly in 
      adipocytes, and HFD-induced obesity tended to increase the ratio of TIMP4 to MMP3 
      protein in females, whereas it decreased it in males. Overexpression of Mmp3 in 
      3T3-L1 preadipocytes or rhMMP3 protein added to primary human preadipocytes 
      inhibited differentiation, whereas rhTIMP4 improved adipogenesis and attenuated 
      the inhibitory effect of rhMMP3. These data suggest that HFD-induced obesity 
      downregulates APC MMP3 expression to trigger adipogenesis, and adipocyte TIMP4 
      may modulate this process to regulate hyperplastic vs. hypertrophic adipose 
      tissue expansion, fat distribution, and metabolic health in a sex- and 
      depot-dependent manner.
CI  - Copyright (c) 2017 the American Physiological Society.
FAU - Wu, Yuanyuan
AU  - Wu Y
AD  - Obesity Center, Department of Medicine, Boston University School of Medicine, 
      Boston, Massachusetts.
FAU - Lee, Mi-Jeong
AU  - Lee MJ
AD  - Obesity Center, Department of Medicine, Boston University School of Medicine, 
      Boston, Massachusetts.
FAU - Ido, Yasuo
AU  - Ido Y
AD  - Obesity Center, Department of Medicine, Boston University School of Medicine, 
      Boston, Massachusetts.
FAU - Fried, Susan K
AU  - Fried SK
AD  - Obesity Center, Department of Medicine, Boston University School of Medicine, 
      Boston, Massachusetts susan.fried@mssm.edu.
LA  - eng
GR  - R24 DK087669/DK/NIDDK NIH HHS/United States
GR  - R01 DK080448/DK/NIDDK NIH HHS/United States
GR  - P30 DK046200/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20161122
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.17 (Mmp3 protein, mouse)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/drug effects/*metabolism/pathology
MH  - Adipogenesis/drug effects
MH  - Adipose Tissue/*growth & development
MH  - Animals
MH  - Cell Differentiation/drug effects/genetics
MH  - Diet, Fat-Restricted
MH  - *Diet, High-Fat
MH  - Female
MH  - Humans
MH  - Hyperplasia
MH  - Hypertrophy
MH  - Male
MH  - Matrix Metalloproteinase 3/*genetics/metabolism/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Obesity/*genetics/metabolism
MH  - RNA, Messenger/*metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Tissue Inhibitor of Metalloproteinases/*genetics/metabolism/pharmacology
MH  - Tissue Inhibitor of Metalloproteinase-4
PMC - PMC5283879
OTO - NOTNLM
OT  - adipocyte size
OT  - adipose progenitor
OT  - hyperplasia
OT  - matrix metalloproteinase 3
OT  - tissue inhibitor of matrix metalloproteinase 4
EDAT- 2016/11/24 06:00
MHDA- 2017/06/21 06:00
PMCR- 2018/01/01
CRDT- 2016/11/24 06:00
PHST- 2016/04/01 00:00 [received]
PHST- 2016/10/26 00:00 [revised]
PHST- 2016/11/08 00:00 [accepted]
PHST- 2016/11/24 06:00 [pubmed]
PHST- 2017/06/21 06:00 [medline]
PHST- 2016/11/24 06:00 [entrez]
PHST- 2018/01/01 00:00 [pmc-release]
AID - ajpendo.00128.2016 [pii]
AID - E-00128-2016 [pii]
AID - 10.1152/ajpendo.00128.2016 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2017 Jan 1;312(1):E58-E71. doi: 
      10.1152/ajpendo.00128.2016. Epub 2016 Nov 22.