The Transcription Factor HOXA5 : Novel Insights into Metabolic Diseases and Adipose Tissue Dysfunction.
Luca ParrilloRosa SpinelliMichele LongoFederica ZatteraleGianluca SantamariaAlessia LeoneMichele CampitelliGregory Alexander RacitiFrancesco BeguinotPublished in: Cells (2023)
The transcription factor HOXA5 , from the HOX gene family, has long been studied due to its critical role in physiological activities in normal cells, such as organ development and body patterning, and pathological activities in cancer cells. Nonetheless, recent evidence supports the hypothesis of a role for HOXA5 in metabolic diseases, particularly in obesity and type 2 diabetes (T2D). In line with the current opinion that adipocyte and adipose tissue (AT) dysfunction belong to the group of primary defects in obesity, linking this condition to an increased risk of insulin resistance (IR) and T2D, the HOXA5 gene has been shown to regulate adipocyte function and AT remodeling both in humans and mice. Epigenetics adds complexity to HOXA5 gene regulation in metabolic diseases. Indeed, epigenetic mechanisms, specifically DNA methylation, influence the dynamic HOXA5 expression profile. In human AT, the DNA methylation profile at the HOXA5 gene is associated with hypertrophic obesity and an increased risk of developing T2D. Thus, an inappropriate HOXA5 gene expression may be a mechanism causing or maintaining an impaired AT function in obesity and potentially linking obesity to its associated disorders. In this review, we integrate the current evidence about the involvement of HOXA5 in regulating AT function, as well as its association with the pathogenesis of obesity and T2D. We also summarize the current knowledge on the role of DNA methylation in controlling HOXA5 expression. Moreover, considering the susceptibility of epigenetic changes to reversal through targeted interventions, we discuss the potential therapeutic value of targeting HOXA5 DNA methylation changes in the treatment of metabolic diseases.
Keyphrases
- insulin resistance
- dna methylation
- adipose tissue
- high fat diet induced
- long non coding rna
- type diabetes
- gene expression
- long noncoding rna
- metabolic syndrome
- genome wide
- high fat diet
- skeletal muscle
- transcription factor
- weight loss
- polycystic ovary syndrome
- poor prognosis
- glycemic control
- weight gain
- copy number
- physical activity
- healthcare
- endothelial cells
- cell proliferation
- signaling pathway
- induced apoptosis
- combination therapy
- fatty acid