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Updated: Feb 25, 2026
Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT
Published on: January 7, 2018
8-Hydroxy-2-deoxyguanosine ameliorates high-fat diet-induced insulin resistance and adipocyte dysfunction in mice
Joo Young Huh1, Inji Jung2, Lingjuan Piao2
1College of Pharmacy, Chonnam National University, Gwangju, Republic of Korea.
Abstract:
8-Hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, has been recently shown to exert anti-inflammatory effects through inhibition of Rac1. Inflammation in adipose tissue is a hallmark of obesity-induced insulin resistance, but the therapeutic potential of 8-OHdG in treatment of metabolic diseases has not been fully elucidated. The aim of this study was to examine the effect of exogenously administered 8-OHdG on adipose tissue and whole body metabolism. In cultured adipocytes, 8-OHdG inhibited adipogenesis and reversed TNFα-induced insulin resistance. In high-fat diet (HFD)-induced obese mice, 8-OHdG administration blunted the rise in body weight and fat mass. The decrease in adipose tissue mass by 8-OHdG was due to reduced adipocyte hypertrophy through induction of adipose triglyceride lipase and inhibition of fatty acid synthase expression. 8-OHdG also inhibited the infiltration of macrophages, resulting in amelioration of adipose tissue inflammation and adipokine dysregulation. Moreover, 8-OHdG administration ameliorated adipocyte as well as systemic insulin sensitivity. Both in vivo and in vitro results showed that 8-OHdG induces AMPK activation and reduces JNK activation in adipocytes. In conclusion, our results show that orally administered 8-OHdG protects against HFD-induced metabolic disorders by regulating adipocyte metabolism.
Insights
8-Hydroxy-2-deoxyguanosine (8-OHdG) reduces body weight and fat mass in obese mice. This oxidative DNA damage marker also improves insulin sensitivity and combats inflammation, offering therapeutic potential for metabolic disorders.
Area of Science:
- Biochemistry
- Metabolic Disease Research
- Molecular Biology
Background:
- Obesity-induced adipose tissue inflammation is linked to insulin resistance.
- 8-Hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, exhibits anti-inflammatory properties.
- The therapeutic role of 8-OHdG in metabolic diseases requires further investigation.
Purpose of the Study:
- To investigate the effects of exogenous 8-OHdG on adipose tissue and overall metabolism.
- To evaluate 8-OHdG's potential in treating obesity-related metabolic dysfunction.
Main Methods:
- In vitro studies using cultured adipocytes.
- In vivo experiments with high-fat diet (HFD)-induced obese mice.
- Analysis of adipocyte metabolism, inflammation markers, and insulin sensitivity.
Main Results:
- 8-OHdG inhibited adipogenesis and reversed TNFα-induced insulin resistance in adipocytes.
- Oral 8-OHdG administration reduced body weight and fat mass in HFD-fed mice.
- 8-OHdG decreased adipocyte size, reduced macrophage infiltration, and improved insulin sensitivity by activating AMPK and inhibiting JNK.
Conclusions:
- Exogenously administered 8-OHdG demonstrates protective effects against HFD-induced metabolic disorders.
- 8-OHdG regulates adipocyte metabolism, reduces inflammation, and enhances insulin sensitivity.
- 8-OHdG holds promise as a therapeutic agent for metabolic diseases associated with obesity.
