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GATA-3 Suppression by DNAzyme Modulates Interleukin-10 and Liver Injury Markers in db/db Mice
by
, , , , , , , , and
Layla Al-Mansoori
1, 
Asma A. Elashi
1,
Laila Hedaya
1,
Maha Alser
1,
Shamma Almuraikhy
1,
Najeha Anwardeen
1,
Hend Al-Jaber
1,
Suhad Hussain
1,
Hamda A. Al-Naemi
2,3,
Vijay Govindharajan
2,
Rafif Mahmood Al-Saady
4,
Mohammed Imad Malki
4,
Khaled Naja
1
and
Mohamed A. Elrayess
1,4,*
1
Biomedical Research Center, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
2
Laboratory Animal Research Centre, Qatar University, Doha P.O. Box 2713, Qatar
3
Department of Biological and Environmental Sciences, Qatar University, Doha P.O. Box 2713, Qatar
4
College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
*
Author to whom correspondence should be addressed.
Biology 2026, 15(1), 89; https://doi.org/10.3390/biology15010089 (registering DOI)
Submission received: 12 November 2025
/
Revised: 19 December 2025
/
Accepted: 29 December 2025
/
Published: 31 December 2025
(This article belongs to the Special Issue Molecular Basis of Metabolic Homeostasis)
Simple Summary
Obesity often leads to liver problems and inflammation, which can worsen conditions like type 2 diabetes. This study explores whether reducing the activity of an intracellular protein called GATA-3, which is involved in fat cell development and inflammation, might offer benefits. We treated obese diabetic mice with a special enzyme-based treatment that targets GATA-3. We found that the treatment did not change how fat was distributed in the body, but it did reduce signs of liver damage and increase levels of an anti-inflammatory protein called interleukin-10. Our results suggest that targeting GATA-3 could be a promising way to protect the liver and reduce inflammation in obesity-related diseases, potentially leading to new treatments for conditions like fatty liver disease and diabetes.
Abstract
Obesity plays a crucial role in the progression of insulin resistance and type 2 diabetes which are related to inflammation and liver disease. GATA-3 is a transcription factor that is involved in adipogenesis and inflammation. Therefore, it could be a potential therapeutic target for obesity-associated metabolic disorders. This study aimed to examine the effects of GATA-3 suppression on body weight, fat depot redistribution, liver histopathology, and inflammatory markers in transgenic db/db obese mice. Male db/db mice received subcutaneous injections of GATA-3-specific DNAzyme (hgd40; 10 or 100 µg/mL), pioglitazone (as a positive control), or vehicle only (as a negative control), twice weekly for two weeks. Body weight, organ weights, liver histopathology, mRNA expression of selected genes and serum cytokine levels were assessed. GATA-3 expression was not region specific, and its suppression did not significantly affect fat depot distribution or organ weights. However, the low dose of hgd40 accelerated body weight gain transiently. It also increased Il10 mRNA expression in the liver and significantly increased IL-10 protein concentration in the serum. In addition, a high dose of hgd40 resulted in a marked decrease in hepatocyte ballooning degeneration. These findings suggest that GATA-3 suppression may modulate inflammation and liver injury in obesity, warranting further investigation into its therapeutic potential for obesity-related metabolic disorders.
Keywords:
obesity; Type 2 diabetes; GATA-3; db/db mice; adipogenesis
