MicroRNA-125a-3p expression in abdominal adipose tissues is associated with insulin signalling gene expressions in morbid obesity: observations in Taiwanese

Asia Pac J Clin Nutr. 2014;23(2):331-7. doi: 10.6133/apjcn.2014.23.2.20.

Abstract

Background: Micro (mi) RNAs have been found to play an important role in the regulation of adipogenesis and insulin sensitivity. However, associations between miRNA and insulin signalling-related gene expressions in abdominal adipose tissues in obese subjects remain unclear.

Methods: We used a microarray platform to screen miRNA expressions in abdominal adipose tissues between genders in severely obese subjects and found that the top-ranking miRNA in abdominal omental adipose tissues was miRNA-125a-3p. MicroR-125a-3p and insulin signalling-related gene expressions in abdominal omental adipose tissues of all subjects (11 men and 10 women) were subsequently quantified by a real-time PCR. Also, associations of miR-125a-3p with insulin signalling-related gene expression and biochemical markers in obese subjects were analyzed by a linear regression analysis.

Results: miR-125a-3p expressed by abdominal omental adipose tissues was much higher in obese men than women. No gender difference was observed in abdominal subcutaneous adipose tissues. Concomitant with high miR-125a-3p, c-Jun N-terminal kinase gene expression was also higher, whereas insulin receptor was lower in men than women. There were negative associations of miR-125a-3p with the insulin receptor and phosphatidylinositol 3-kinase expressions. Fasting plasma glucose and cholesterol levels were positively associated with miR- 125a-3p expression. These associations were obvious in obese men but not women.

Conclusion: Our results support the involvement of miR-125a-3p in regulating the insulin signalling pathway and imply that increased miR- 125a-3p expression in omental adipose tissues may be a characteristic feature of insulin resistance in obese men.

背景:微形核糖核酸(miRNA)在調節脂肪生合成及胰島素抗性扮演重要角色, 但是肥胖者腹腔脂肪組織miRNA 與胰島素訊息傳遞相關基因表現之間的相關 性仍不確知。方法: 本研究利用微陣列的平台來篩檢不同性別重度肥胖者腹腔 脂肪組織中miRNA 的表現,發現在腹腔網膜脂肪表現量最高的是miRNA- 125a-3p,所以我們再用即時聚合酶鏈鎖反應確認並定量所有肥胖者(11 位男性 及10 位女性)腹腔網膜脂肪中miRNA-125a-3p 及胰島素訊息傳遞相關基因的 表現,同時也以線性迴歸法分析miRNA-125a-3p 與胰島素訊息傳遞相關基因 表現及血中生化指標間的相關性。結果: 肥胖男性腹腔網膜脂肪miRNA-125a- 3p 的表現較女性為高,腹腔皮下脂肪則無性別間之差異,有高miRNA-125a- 3p 表現量的肥胖男性,其c-Jun N-terminal kinase 的基因表現量也會高,而胰 島素接受器的表現量則較肥胖女性為低。miRNA-125a-3p 與胰島素接受器及 phosphatidylinositol 3-kinase 的表現成負相關, 而空腹血糖和膽固醇值與 miRNA-125a-3p 的表現則成正相關。這些相關性在肥胖男性很顯著,但在肥胖 女性則不明顯。結論:本研究結果顯示miRNA-125a-3p 參與了胰島素訊息傳遞 路徑的調節,而腹腔網膜脂肪miRNA-125a-3p 表現量增加可能是肥胖男性胰 島素抗性的一個表徵。

MeSH terms

  • Abdominal Fat / metabolism*
  • Adult
  • Blood Glucose
  • Cholesterol
  • Female
  • Gene Expression / genetics*
  • Humans
  • Insulin / genetics*
  • Insulin / metabolism
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Microarray Analysis / methods
  • Middle Aged
  • Obesity, Morbid / genetics*
  • Obesity, Morbid / metabolism
  • Polymerase Chain Reaction / methods
  • Sex Factors
  • Signal Transduction / genetics*
  • Taiwan
  • Young Adult

Substances

  • Blood Glucose
  • Insulin
  • MIRN125 microRNA, human
  • MicroRNAs
  • Cholesterol