3-Amino-1,2,4-Triazole Induces Quick and Strong Fat Loss in Mice with High Fat-Induced Metabolic Syndrome
Valéria Nunes-Souza1,2,3,4, Nelson Miguel Dias-Júnior1,2, Marcos Antônio Eleutério-Silva1,2,5
1Laboratório de Reatividade Cardiovascular, Setor de Fisiologia, Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Alagoas, Maceió, Alagoas, Brazil.
Background:
Obesity is a growing epidemic with limited effective treatments and an important risk factor for several diseases such as metabolic syndrome (MetS). In this study, we aimed to investigate the effect of 3-amino-1,2,4-triazole (ATZ), an inhibitor of catalase and heme synthesis, in a murine model for MetS.
Methods:
Male C57BL/6 mice with high-fat diet-induced MetS received ATZ (500 mg·kg-1·24 h-1) for 12 weeks.
Results:
The HFD group showed increased blood pressure and body weight, enhanced fat deposition accompanied by an increase in adipocyte diameter, and decreased lipolysis in white adipose tissue (WAT). The expression of genes related to inflammation was increased in WAT of the HFD group. Concurrently, these mice exhibited an increase in leptin, nonesterified fatty acid (NEFA), insulin, and glucose in plasma, coupled with glucose intolerance and insulin resistance. Strikingly, ATZ prevented the increase in blood pressure and the HFD-induced obesity as observed by lower body weight, WAT index, triglycerides, NEFA, and leptin in plasma. ATZ treatment also prevented the HFD-induced increase in adipocyte diameter and even induced marked atrophy and the accumulation of macrophages in this tissue. ATZ treatment also improved glucose metabolism by increasing glucose tolerance and insulin sensitivity, GLUT4 mRNA expression in WAT in parallel to decreased insulin levels.
Conclusions:
In the context of HFD-induced obesity and metabolic syndrome, the fat loss induced by ATZ is probably due to heme synthesis inhibition, which blocks adipogenesis by probably decreased RevErbα activity, leading to apoptosis of adipocytes and the recruitment of macrophages. As a consequence of fat loss, ATZ elicits a beneficial systemic antiobesity effect and improves the metabolic status.
Insights
3-amino-1,2,4-triazole (ATZ) reduced obesity and metabolic syndrome in mice by inhibiting heme synthesis, leading to fat loss and improved insulin sensitivity. This study highlights ATZ
Area of Science:
- Biochemistry and Metabolism
- Obesity Research
- Pharmacology
Background:
- Obesity is a global health crisis and a major risk factor for metabolic syndrome (MetS).
- Current treatments for obesity and MetS are limited in efficacy.
- 3-amino-1,2,4-triazole (ATZ), a catalase and heme synthesis inhibitor, was investigated for its potential effects on MetS.
Purpose of the Study:
- To evaluate the therapeutic effect of ATZ in a mouse model of diet-induced metabolic syndrome.
- To elucidate the mechanisms underlying ATZ's action on adipose tissue and metabolic parameters.
Main Methods:
- Male C57BL/6 mice were fed a high-fat diet (HFD) to induce MetS.
- ATZ (500 mg·kg⁻¹·24h⁻¹) was administered to HFD-fed mice for 12 weeks.
- Physiological, biochemical, and molecular analyses were performed on adipose tissue and plasma.
Main Results:
- HFD induced obesity, hypertension, insulin resistance, and inflammation in white adipose tissue (WAT).
- ATZ treatment prevented HFD-induced weight gain, reduced adipocyte size, and decreased fat accumulation.
- ATZ improved glucose tolerance, insulin sensitivity, and reduced plasma leptin and triglycerides.
Conclusions:
- ATZ treatment ameliorates diet-induced obesity and metabolic syndrome in mice.
- Fat loss induced by ATZ is linked to heme synthesis inhibition, blocking adipogenesis and promoting adipocyte apoptosis.
- ATZ demonstrates potential as an anti-obesity agent with beneficial metabolic effects.
![Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [18F]FDG Micro-PET/MR Imaging](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F62460.jpg&w=3840&q=50)