Inhibition of Tropomyosin Receptor Kinase B Signaling Alters Hepatic Mitochondrial Enzyme Activity and Oxidative Stress in Mice With Sucrose‐Induced Insulin Resistance
TL;DR
Findings indicate that TrkB inhibition may influence selected hepatic mitochondrial enzyme activities and redox‐related markers under sucrose‐induced metabolic stress, however, these results should be interpreted cautiously because systemic insulin resistance markers were not significantly improved, and additional control groups are required to clarify ANA‐12‐specific and vehicle‐related effects.
Abstract
ABSTRACT BDNF and its receptor, TrkB, are essential regulators of energy homeostasis in both central and peripheral tissues, including the liver. This study aimed to investigate the effects of ANA‐12, a selective TrkB antagonist, on hepatic mitochondrial enzyme activities and biochemical parameters in a mouse model of sucrose‐induced insulin resistance. Male C57BL/6J mice were divided into four groups: Control, Sucrose (35% solution), Sucrose+DMSO, and Sucrose+ANA‐12 (0.5 mg/kg). Following a 16‐week dietary intervention, ANA‐12 was administered via intraperitoneal injection during the final 21 days. Hepatic activities of cytochrome c oxidase, superoxide dismutase (SOD), and catalase (CAT), along with malondialdehyde (MDA) levels, were analyzed to evaluate mitochondrial enzyme activity and oxidative stress‐related biochemical changes. Chronic sucrose consumption significantly increased body weight, serum insulin levels, HOMA‐IR scores, and cholesterol levels. While ANA‐12 treatment showed a numerical tendency to attenuate weight gain and HOMA‐IR scores, these changes did not reach statistical significance. However, the ANA‐12 group exhibited significantly lower serum leptin and ceramide levels compared to the Sucrose+DMSO group. In the liver, sucrose consumption triggered oxidative stress, as evidenced by increased MDA levels. Conversely, TrkB inhibition was associated with increased cytochrome c oxidase activity, altered SOD activity, and reduced hepatic MDA concentrations compared with the Sucrose+DMSO group, suggesting partial modulation of oxidative stress‐related biochemical alterations. Furthermore, chronic sucrose consumption was associated with reduced hepatic BDNF levels. Overall, these findings indicate that TrkB inhibition may influence selected hepatic mitochondrial enzyme activities and redox‐related markers under sucrose‐induced metabolic stress. However, these results should be interpreted cautiously because systemic insulin resistance markers were not significantly improved, and additional control groups are required to clarify ANA‐12‐specific and vehicle‐related effects.