Obesity is defined as excessive fat accumulation in adipose tissue and has an unclear pathogenesis.
Obesity is an epidemic health problem worldwide and a major contributor to metabolic syndrome and disorders, such as type II diabetes, nonalcoholic fatty liver disease, cardiovascular disease, and some cancers.
Mammals have three types of adipocytes: white, classical brown, and beige adipocytes. White adipocytes specialize in energy storage, while brown adipocytes specialize in energy expenditure without generating ATP. In addition to the classical brown adipocytes, beige adipocytes represent UCP1-expressing brown adipocytes emerging in white adipose tissue upon certain stimulations.
MicroRNAs - active molecules for obesity
MicroRNAs (miRNAs) are a novel group of small noncoding RNAs that emerge as important regulators of mRNA expression. Increasing evidence has demonstrated that plenty of miRNAs play a role in obesity through regulating adipogenesis.
Adipogenesis is a complex process and contains two main stages, commitment and differentiation. miRNAs have been reported to modulate adipocyte differentiation by targeting adipogenic regulators.
For example, miR-143 enhances the differentiation of cultured human preadipocytes and directly targets FGF7 which may function as a fine-tuning molecule in the adipogenic process. Similarly, miR-27b directly targets PPARγ and inhibits the process of human adipogenesis.
The evidence suggests that different miRNAs have different effects on adipocyte differentiation. However which adipocyte-specific genes are regulated by specific miRNA is not clear so far.
Currently, circulating miRNAs are treated as potential biomarkers for obesity. For example, miR-223, miR-15b, and miR-130b increase in overweight people with obesity. However, it remains unclear whether adipocyte-functioned miRNAs will become novel biomarkers for obesity.
Researchers from Shanghai Institute of Endocrine and Metabolic Diseases.have investigated the regulating functions of a miR-129-5p in adipogenesis in vitro and have explored its possible role in the pathogenesis of obesity in humans. Based on their study, the direct target genes of miR-129-5p were identified along with the possible signaling pathway mediating adipocyte differentiation and the browning program of white adipocytes.
Moreover, this research group explored the associations between circulating miR-129-5p and parameters of obesity and aimed to provide novel therapeutic targets for defeating obesity.
The miRNAs expression was detected in obese mouse models (db/db) and wild-type mice. miR-129-5p was highly expressed in obese mice. Relative expression level of all measured miRNAs in obese mice was higher compared with wild-type mice (n = 10; p < 0.01).
Their studies also show that miR-129-5p could significantly inhibit adipocyte differentiation and white adipocyte browning in vitro and decreases the level of specific adipose markers, such as FABP4, UCP1, and PPARγ, in mature white and brown adipocytes. miR-129-5p directly targets the ATG7gene which is predicted with bioinformatics and confirmed by dual-luciferase reporter assay.
Serum miR-129-5p in Humans.
To confirm whether miR-129-5p plays an important role in humans with obesity, they measured the serum level of miR-129-5p in 15 normal weight participants and 16 patients with simple obesity and analyzed the correlation between serum miR-129-5p with obesity indices.
As they expected, the miR-129-5p level was elevated in patients with simple obesity compared with the normal weight subjects (p < 0.01).
Interestingly, a positive correlation between miR-129-5p level and obesity indices was evident, including BMI and fat percentage, suggesting a link between obesity and miR-129-5p level.
Taken together, these results demonstrated that circulating miR-129-5p might be a potential therapeutic target for obesity and related metabolic disorders and biomarker for obesity in humans.
Sources: International Journal of Endocrinology., DOI: 10.1155/2019/5069578
MSc. Lenka Chalupová, Ph.D., Senior Researcher