PMID- 25441253
OWN - NLM
STAT- MEDLINE
DCOM- 20160226
LR  - 20191113
IS  - 2212-3873 (Electronic)
IS  - 1871-5303 (Linking)
VI  - 15
IP  - 2
DP  - 2015
TI  - Thalidomide controls adipose tissue inflammation associated with high-fat 
      diet-induced obesity in mice.
PG  - 151-8
AB  - INTRODUCTION: Immunosuppressant agents modulate the activity of the immune system 
      and control adipose tissue inflammatory responses associated with obesity. 
      Controlling adipose tissue inflammation represents an interesting option for 
      inhibiting the low-grade inflammatory state in obese subjects and for preventing 
      obesity-associated pathologies. In this work, we assessed the effects of 
      thalidomide on the inflammatory response in adipose tissue as well as on systemic 
      inflammatory marker expression in the well-established high-fat diet-induced 
      obesity mouse model. METHODS: Swiss male mice were fed a high-fat diet (60% kcal 
      from fat) for 12 weeks and received thalidomide for the last 10 days (100 
      mg.kg-1). Adipokine levels were measured in serum and adipose tissue by EIA and 
      real-time quantitative PCR, respectively. Adipose tissue infiltrating macrophages 
      were identified by immunohistochemistry and western blot analysis of F4/80 marker 
      expression. Other inflammatory markers, such as c-Jun N-terminal kinase (JNK) 
      phosphorylation and monocyte chemoattractant protein-1 (MCP-1) production, were 
      also evaluated by western blot analysis. In vitro assays using 3T3-L1 adipocytes 
      were also conducted to evaluated adipokine release. RESULTS: In obese mice, 
      thalidomide administration induced a reduction in adiposity accompanied by a 
      reduction of tumor necrosis factor-alpha (TNF-alpha), leptin and MCP-1 adipose tissue 
      production, macrophage infiltration and JNK activation. TNF-alpha and leptin serum 
      levels were also reduced by thalidomide treatment in obese mice. In vitro, the 
      release of basal TNF-alpha and lipopolysaccharide (LPS)-induced MCP-1 was inhibited 
      in 3T3-L1 cells. SIGNIFICANCE: Our results suggest that drugs that can modulate 
      the inflammatory status as well as control adipose tissue expansion could 
      represent an interesting approach in the management of obesity, highlighting the 
      need for further development of such compounds.
FAU - Nakamitsu, Patricia Z
AU  - Nakamitsu PZ
FAU - Compri, Cecilia M
AU  - Compri CM
FAU - de Fraia Pinto, Livia
AU  - de Fraia Pinto L
FAU - Gotardo, Erica M F
AU  - Gotardo EM
FAU - de Oliveira, Caroline C
AU  - de Oliveira CC
FAU - Ribeiro, Marcelo L
AU  - Ribeiro ML
FAU - Pedrazzoli, Jose Jr
AU  - Pedrazzoli J Jr
FAU - Gambero, Alessandra
AU  - Gambero A
AD  - Clinical Pharmacology and Gastroenterology Unit, Sao Francisco University Medical 
      School, Av. Sao Francisco de Assis 218, 12916-900, Braganca Paulista, SP, Brazil. 
      alessandra.gambero@usf.edu.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Endocr Metab Immune Disord Drug Targets
JT  - Endocrine, metabolic & immune disorders drug targets
JID - 101269157
RN  - 0 (Adipokines)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipogenesis/drug effects
MH  - Adipokines/blood/genetics
MH  - Adipose Tissue/*drug effects/immunology/metabolism
MH  - Adiposity/drug effects
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Cytokines/metabolism
MH  - *Diet, High-Fat
MH  - Disease Models, Animal
MH  - Inflammation Mediators/blood
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Macrophages/drug effects/immunology/metabolism
MH  - Male
MH  - Mice
MH  - Obesity/*drug therapy/genetics/immunology/metabolism
MH  - Panniculitis/genetics/immunology/metabolism/*prevention & control
MH  - Phosphorylation
MH  - Signal Transduction/drug effects
MH  - Thalidomide/*pharmacology
MH  - Time Factors
EDAT- 2014/12/03 06:00
MHDA- 2016/02/27 06:00
CRDT- 2014/12/03 06:00
PHST- 2014/08/12 00:00 [received]
PHST- 2014/11/12 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2016/02/27 06:00 [medline]
AID - EMIDDT-EPUB-63658 [pii]
AID - 10.2174/1871530314666141128115225 [doi]
PST - ppublish
SO  - Endocr Metab Immune Disord Drug Targets. 2015;15(2):151-8. doi: 
      10.2174/1871530314666141128115225.