AGER-1 Long Non-Coding RNA Levels Correlate with the Expression of the Advanced Glycosylation End-Product Receptor, a Regulator of the Inflammatory Response in Visceral Adipose Tissue of Women with Obesity and Type 2 Diabetes Mellitus.

Abstract

The advanced glycosylation end-product receptor (AGER) is involved in the development of metabolic inflammation and related complications in type 2 diabetes mellitus (T2DM). Tissue expression of the AGER gene (AGER) is regulated by epigenetic mediators, including a long non-coding RNA AGER-1 (lncAGER-1). This study aimed to investigate whether human obesity and T2DM are associated with an altered expression of AGER and lncAGER-1 in adipose tissue and, if so, whether these changes affect the local inflammatory milieu. The expression of genes encoding AGER, selected adipokines, and lncAGER-1 was assessed using real-time PCR in visceral (VAT) and subcutaneous (SAT) adipose tissue. VAT and SAT samples were obtained from 62 obese (BMI > 40 kg/m2; N = 24 diabetic) and 20 normal weight (BMI = 20-24.9 kg/m2) women, while a further 15 SAT samples were obtained from patients who were 18 to 24 months post-bariatric surgery. Tissue concentrations of adipokines were measured at the protein level using an ELISA-based method. Obesity was associated with increased AGER mRNA levels in SAT compared to normal weight status (p = 0.04) and surgical weight loss led to their significant decrease compared to pre-surgery levels (p = 0.01). Stratification by diabetic status revealed that AGER mRNA levels in VAT were higher in diabetic compared to non-diabetic women (p = 0.018). Elevated AGER mRNA levels in VAT of obese diabetic patients correlated with lncAGER-1 (p = 0.04, rs = 0.487) and with interleukin 1β (p = 0.008, rs = 0.525) and resistin (p = 0.004, rs = 0.6) mRNA concentrations. In conclusion, obesity in women is associated with increased expression of AGER in SAT, while T2DM is associated with increased AGER mRNA levels and pro-inflammatory adipokines in VAT.

• Authors: Klaudia Gutowska, Krzysztof Koźniewski, Michał Wąsowski, Marta Izabela Jonas, Zbigniew Bartoszewicz, Wojciech Lisik, Maurycy Jonas, Artur Binda, Paweł Jaworski, Wiesław Tarnowski, Bartłomiej Noszczyk, Monika Puzianowska-Kuźnicka, Krzysztof Czajkowski, Alina Kuryłowicz
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 24 Issue 24 (Dec 13 2023) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 38139276 (Publication Type: Journal Article)

Chemical References

• RNA, Long Noncoding
• Adipokines
• Glycation End Products, Advanced
• RNA, Messenger

Topics

• Humans
• Female
• RNA, Long Noncoding (genetics, metabolism)
• Diabetes Mellitus, Type 2 (complications, genetics, metabolism)
• Intra-Abdominal Fat (metabolism)
• Obesity (complications, genetics, metabolism)
• Adipose Tissue (metabolism)
• Adipokines (genetics, metabolism)
• Glycation End Products, Advanced (metabolism)
• RNA, Messenger (genetics, metabolism)
• Subcutaneous Fat (metabolism)