Sex- and Dose-Dependent Effect of L-Citrulline on Body Weight and Food Intake in Obese Type 2 Diabetic Rats

Obesity and type 2 diabetes (T2D) are associated with nitric oxide (NO) deficiency. L-citrulline (Cit), a substrate for NO synthesis, has been suggested as a treatment for obesity and T2D.

This study aims to determine the effects of Cit on body weight, food intake, and water consumption in obese T2D male and female rats.

The T2D was induced using a high-fat diet (HFD) and a low dose of streptozotocin (STZ). Obese male (n = 30) and female (n = 30) rats with T2D were divided into five groups (n = 6/group) that received Cit (0, 1, 4, 7, and 10 g/L in drinking water for 8 weeks). Body weight, food intake, and water consumption were measured every week. Serum Cit and nitrite+nitrate (NOx) concentrations were measured at weeks 0, 4, and 8, and serum fasting glucose was measured at week 8.

Compared to non-treated T2D rats, Cit-treated male rats had lower body weight (11.3%, 13.0%, and 11.6% at doses of 4, 7, and 10 g/L), lower food intake (4.7% and 5.5% at doses of 4 and 7 g/L), and water consumption (7% at dose 7 g/L). In female rats, Cit decreased body weight (7.2%, 8%, and 7.3% at doses of 4, 7, and 10 g/L), food intake (4.0% and 5.0% at doses of 4 and 7 g/L), and water consumption (5% and 6.6% at doses of 4 and 7 g/L; all P < 0.001). The body weight and food intake-lowering effects of Cit were higher in T2D male rats than females (all P < 0.05), but decreased water consumption was comparable between sexes. A Cit dose of 7 g/L was most effective in reducing all measured parameters in both sexes.

The Cit decreased body weight, food intake, and water consumption in obese T2D male and female rats. These effects were sex- and dose-dependent.