Sibutramine high-doses effects in cafeteria diet-induced obese rats

Obesity, defined as excessive fat accumulation that impairs health, is a global challenge with high mortality rates. Sibutramine, a centrally acting anorectic, was widely used in obesity treatment due to its effects on appetite control and weight loss. It represented a key step in anti-obesity pharmacotherapy before being withdrawn in many countries. This study evaluates how a high sibutramine dose (10 mg.kg.day^-1 followed by 13 mg.kg.day^-1) influences body weight, biochemical profiles, liver and intestinal health, and gut microbiota composition in rats subjected to a cafeteria diet for 16 weeks. Rats treated with sibutramine exhibited a 10.93% reduction in body weight and improved glycemic control compared to untreated groups. Sibutramine modulated lipid profiles by lowering total cholesterol and increasing HDL levels in controlled diet groups. The treatment attenuated liver damage markers (AST and ALT) and increased intestinal crypt depth, suggesting gut integrity. The elevated sibutramine dose led to distinct microbiota shifts, partially reversing cafeteria diet-induced dysbiosis by increasing SCFA-producing genera, including Bacillus, Marvinbryantia, and Bifidobacterium. However, dietary factors remained the dominant driver of microbial composition. These findings underscore the impact of sibutramine's dosing on gut microbiota and reinforce its role in obesity-related health improvements.