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. 2024 Oct 9:15:1468824.
doi: 10.3389/fendo.2024.1468824. eCollection 2024.

Exploring lipodystrophy gene expression in adipocytes: unveiling insights into the pathogenesis of insulin resistance, type 2 diabetes, and clustering diseases (metabolic syndrome) in Asian Indians

Aditya Saxena  1 , Pradeep Tiwari  2 , Shalu Gupta  3 , Rajendra Mandia  3 , Ramesh C Banshiwal  4 , Ravinder Kumar Lamoria  4 , Ranjit Mohan Anjana  5 , Venkatesan Radha  5 , Viswanathan Mohan  5 , Sandeep Kumar Mathur  6
Affiliations

Exploring lipodystrophy gene expression in adipocytes: unveiling insights into the pathogenesis of insulin resistance, type 2 diabetes, and clustering diseases (metabolic syndrome) in Asian Indians

Aditya Saxena et al. Front Endocrinol (Lausanne). .

Abstract

Background: Studying the molecular mechanisms of lipodystrophy can provide valuable insights into the pathophysiology of insulin resistance (IR), type 2 diabetes (T2D), and other clustering diseases [metabolic syndrome (MetS)] and its underlying adipocentric disease (MetS disease).

Methods: A high-confidence lipodystrophy gene panel comprising 50 genes was created, and their expressions were measured in the visceral and subcutaneous (both peripheral and abdominal) adipose depots of MetS and non-MetS individuals at a tertiary care medical facility.

Results: Most lipodystrophy genes showed significant downregulation in MetS individuals compared to non-MetS individuals in both subcutaneous and visceral depots. In the abdominal compartment, all the genes showed relatively higher expression in visceral depot as compared to their subcutaneous counterpart, and this difference narrowed with increasing severity of MetS. Their expression level shows an inverse correlation with T2D, MetS, and HOMA-IR and with other T2D-related intermediate traits. Results also demonstrated that individualization of MetS patients could be done based on adipose tissue expression of just 12 genes.

Conclusion: Adipose tissue expression of lipodystrophy genes shows an association with MetS and its intermediate phenotypic traits. Mutations of these genes are known to cause congenital lipodystrophy syndromes, whereas their altered expression in adipose tissue contributes to the pathogenesis of IR, T2D, and MetS.

Keywords: Asian Indians; adipose tissue; central obesity; insulin resistance; lipodystrophy; metabolic syndrome MetS; qPCR; type 2 diabetes.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Disease–gene network selected lipodystrophy genes.
Figure 2
Figure 2
Fold change of lipodystrophy genes in MetS as compared to non-MetS (normalized to one) among individuals in (A) the visceral depot and in (B) the subcutaneous compartment.
Figure 3
Figure 3
Fold change of lipodystrophy specific genes in abdominal visceral adipose tissue as compared to abdominal subcutaneous adipose tissue in MetS (3+ score) and non-MetS (0–1 score) cohort.
Figure 4
Figure 4
Decision tree generated to classify all the 117 samples into their MetS group in subcutaneous fat.
See this image and copyright information in PMC

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