Diabetes Metab J.  2014 Oct;38(5):356-365. 10.4093/dmj.2014.38.5.356.

Adipose Gene Expression Profiles Related to Metabolic Syndrome Using Microarray Analyses in Two Different Models

• Yoo HJ
• Hwang HJ
• Jung TW
• Ryu JY
• Hong HC
• Choi HY
• Baik SH
• Choi KM

• KMID: 2280680
• DOI: http://doi.org/10.4093/dmj.2014.38.5.356

Abstract

BACKGROUND
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist has a wide-ranging influence on multiple components of metabolic syndrome. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a useful animal model of metabolic syndrome. To determine genes related to metabolic syndrome, we examined overlapping genes that are simultaneously decreased by PPAR-gamma agonists and increased in OLETF rats using microarrays in two different models.
METHODS
In the first microarray analysis, PPAR-gamma agonist-treated db/db mice were compared to standard diet-fed db/db mice. In the second microarray analysis, OLETF rats were compared to Long-Evans Tokushima Otsuka (LETO) rats (control of OLETF rats).
RESULTS
Among the overlapping genes, in the present study, we validated that lipocalin-2 expression was significantly decreased in the visceral adipose tissue of PPAR-gamma agonist-treated db/db mice compared to standard diet-fed db/db mice and increased in OLETF rats compared to LETO rats using real time reverse transcription polymerase chain reaction. Furthermore, we showed for the first time that lipocalin-2 expression was significantly increased in the visceral adipose tissues of obese humans compared with nonobese humans. In addition, the expression level of lipocalin-2 in human visceral adipose tissue had a significant positive correlation with body mass index, serum interleukin-6, adipocyte fatty acid binding protein levels, and white blood cell count.
CONCLUSION
Lipocalin-2 was confirmed to be a significant adipokine affected by PPAR-gamma agonist and obesity in the present study. Also, for the first time in human visceral adipose tissue, it was determined that the expression of lipocalin-2 from obese humans was significantly increased and correlated with circulating inflammatory markers.

Keyword

Lipocalin-2; Microarray; PPAR gamma

MeSH Terms

Adipocytes
Adipokines
Animals
Body Mass Index
Carrier Proteins
Genes, Overlapping
Humans
Interleukin-6
Intra-Abdominal Fat
Leukocyte Count
Mice
Microarray Analysis
Models, Animal
Obesity
Peroxisomes
Polymerase Chain Reaction
PPAR gamma
Rats
Rats, Inbred OLETF
Reverse Transcription
Transcriptome*
Adipokines
Carrier Proteins
Interleukin-6
PPAR gamma

Figure

• 

  Fig. 1 Flow sheet of microarrays in two different models and validation process. PPAR-γ, peroxisome proliferator-activated receptor-γ; OLETF, Otsuka Long-Evans Tokushima Fatty; LETO, Long-Evans Tokushima Otsuka; RT-PCR, reverse transcription polymerase chain reaction.

• 

  Fig. 2 Expression of lipocalin-2 in adipose tissue from independent rodent and human samples. (A) Visceral adipose tissues of 24-week-old male Long-Evans Tokushima Otsuka (LETO) rats (black bars) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats (white bars). (B) Visceral adipose tissues of standard chow-fed db/db mice (black bars) and pioglitazone-treated db/db mice (white bars). (C) Visceral adipose tissues of nonobese women (black bars) and obese women (white bars). (D) Subcutaneous adipose tissues of nonobese women (black bars) and obese women (white bars). Gene expression levels were measured by real time reverse transcription polymerase chain reaction. NS, non significant. aP<0.05, bP<0.01.

• 

  Fig. 3 Spearman correlation coefficient between the level of expression of lipocalin-2 in visceral adipose tissues of humans and (A) body mass index (BMI), (B) white blood cell (WBC) count, (C) serum interleukin-6 (IL-6), and (D) adipocyte fatty acid binding protein (A-FABP) levels. The horizontal axis of each graph indicates the expression ratio of lipocalin-2 versus β-actin in the visceral adipose tissues of humans measured by real time reverse transcription polymerase chain reaction.

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