ATP-binding cassette transporter A1 (ABCA1) expression in adipose tissue and its modulation with insulin resistance in obesity

Abstract

Purpose

Adipose tissue dysfunction is at the center of metabolic dysfunctions associated with obesity. Through studies in isolated adipocytes and mouse models, ATP-binding cassette transporter A1 (ABCA1) expression in the adipose tissue has been shown to regulate high-density lipoprotein (HDL) cholesterol levels in the circulation and insulin sensitivity at both adipose tissue and whole-body levels. We aimed to explore the possible link between ABCA1 expression in the adipose tissue and metabolic derangements associated with obesity in humans.

Patients and methods

This exploratory study among individuals who were lean (body mass index [BMI]: 22.3±0.34 kg/m², n=28) and obese (BMI: 44.48±5.3 kg/m², n=34) compared the expression of ABCA1, adiponectin and GLUT4 (SLC2A4) in visceral and subcutaneous adipose tissue using quantitative real-time PCR and immunohistochemistry. Homeostatic model assessment for insulin resistance (HOMA-IR) and adipose tissue insulin resistance (adipo-IR) were used as insulin resistance markers.

Results

Visceral adipose tissue from individuals who were obese had significantly lower ABCA1 (P=0.04 for mRNA and protein) and adiponectin (P=0.001 for mRNA) expression compared to that from lean individuals. Subcutaneous adipose tissue did not show any significant difference in the expression. When individuals were divided into insulin-sensitive (IS) and insulin-resistant (IR) groups based on HOMA-IR, IR individuals had lower ABCA1 (P=0.0001 for mRNA and P=0.009 for protein) expression compared to IS individuals in visceral adipose tissue, but not in subcutaneous adipose tissue. The difference was significant after adjusting for age, gender and BMI. ABCA1 mRNA expression in visceral adipose tissue correlated negatively with both HOMA-IR (r=−0.44, P=0.0003) and adipo-IR (r=−0.35, P=0.005) after adjusting for age, gender and BMI. ABCA1 expression in either visceral or subcutaneous adipose tissue did not have any significant correlation with HDL cholesterol levels or mean adipocyte area.

Conclusion

Obesity and insulin resistance are associated with lower expression of ABCA1 in visceral adipose tissue in humans.

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Keywords:

• metabolic syndrome
• cholesterol
• diabetes
• adiponectin

Acknowledgments

The authors would like to acknowledge Dr Manjunath Maruti Pol, Dr Harshit Garg and Dr Abhineet KP for helping with the collection of adipose tissue samples and Mr Rintu Kutum for helping with the statistical analysis. Dr Vincent would like to acknowledge the contributions of Dr Anurag Kumar, Dr Ambrish Tiwari and Dr Prajwal Aathreya. This study was supported by an intramural research grant from All India Institute of Medical Sciences, New Delhi to Dr Archna Singh. The sponsors did not have any role in any of the stages from study design to submission of the paper for publication.

Disclosure

The authors report no conflicts of interest in this work.