The Transcription Factor <i>HOXA5</i>: Novel Insights into Metabolic Diseases and Adipose Tissue Dysfunction
Luca Parrillo,
Rosa Spinelli,
Michele Longo,
Federica Zatterale,
Gianluca Santamaria,
Alessia Leone,
Michele Campitelli,
Gregory Alexander Raciti,
Francesco Beguinot
Affiliations
Luca Parrillo
URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy
Rosa Spinelli
URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy
Michele Longo
URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy
Federica Zatterale
URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy
Gianluca Santamaria
Department of Experimental and Clinical Medicine, University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy
Alessia Leone
URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy
Michele Campitelli
URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy
Gregory Alexander Raciti
URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy
Francesco Beguinot
URT Genomics of Diabetes, Institute of Experimental Endocrinology and Oncology, National Research Council, Department of Translational Medical Sciences, Federico II University of Naples, 80131 Naples, Italy
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.
