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

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/m 2 , n=28) and obese (BMI: 44.48±5.3 kg/m 2 , 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.

Serum Adipocytokines Levels and Their Association with Insulin Sensitivity in Morbidly Obese Individuals Undergoing Bariatric Surgery

“…Plasma glucose was estimated using Randox GOD-PAP glucose estimation kit (Randox Laboratories, Crumlin, UK) according to manufacturer’s protocol. 18 Insulin was estimated using chemiluminescence-based immunoassay in a Liaison autoanalyzer (Diasorin, Saluggia, Italy). Serum glycosylated hemoglobin was determined using high performance liquid chromatography.…”

“…Serum glycosylated hemoglobin (HbA1c) was determined using HPLC. 18 To test for associations between the inflammation profile and insulin sensitivity status of the individuals in our study, we used the well-established markers of insulin resistance HOMA-IR, HOMA-β, and QUICKI as useful indices for insulin sensitivity. These indices are calculated parameters and use the value of fasting plasma glucose and insulin for their determination.…”

The impact of ATP-binding cassette transporters on metabolic diseases

“…ABCA1 generally cooperates with ABCG1 and scavenger receptor-BI (SR-BI) to assemble HDL [ 33 ]. The contribution of hepatic and intestinal ABCA1 to the plasma HDL pool is 70–80% and 15–20%, respectively [ 38 ]. In cells, ABCA1 mediates lipid transport between the Golgi and cell membrane [ 39 ].…”

“…In obese adults, adipose tissues usually contain over 50% of the TC in the body [ 39 ]. Obesity is associated with reduced expression of ABCA1 in visceral adipose tissues [ 38 ]. Adipocyte ABCA1 is a key regulator of adipocyte lipogenesis and lipid accretion, likely due to increased cholesterol on adipose tissue membranes.…”

“…It has been confirmed in mouse models that a lack of adipocyte-specific ABCA1 leads to obesity. In addition, these mice without adipocyte-specific ABCA1 also showed decreased levels of the most active form of adiponectin and high-molecular-weight adiponectin [ 38 ]. Furthermore, GPS2 has been found to be downregulated in obese and T2DM subjects, providing additional evidence for the repression of ABCA1 in obesity and T2DM [ 40 ].…”