Anti-obesity and anti-diabetic effects of L-citrulline are sex-dependent.

ABSTRACT

AIMS: Anti-diabetic and anti-obesity effects of L-citrulline (Cit) have been reported in male rats. This study determined sex differences in response to Cit in Wistar rats. MAIN METHODS: Type 2 diabetes (T2D) was induced using a high-fat diet followed by low-dose of streptozotocin (30 mg/kg) injection. Male and female Wistar rats were divided into 4 groups (n = 6/group) Control, control+Cit, T2D, and T2D + Cit. Cit (4 g/L in drinking water) was administered for 8 weeks. Obesity indices were recorded, serum fasting glucose and lipid profile were measured, and glucose and pyruvate tolerance tests were performed during the Cit intervention. White (WAT) and brown (BAT) adipose tissues were weighted, and the adiposity index was calculated at the end of the study. KEY FINDINGS: Cit was more effective in decreasing fasting glucose (18 % vs. 11 %, P = 0.0100), triglyceride (20 % vs. 14 %, P = 0.0173), and total cholesterol (16 % vs. 11 %, P = 0.0200) as well as decreasing gluconeogenesis and improving glucose tolerance, in females compared to male rats with T2D. Following Cit administration, decreases in WAT weight (16 % vs. 14 % for gonadal, 21 % vs. 16 % for inguinal, and 18 % vs. 13 % for retroperitoneal weight, all P < 0.0001) and increases in BAT weight (58 % vs. 19 %, for interscapular and 10 % vs. 7 % for axillary, all P < 0.0001) were higher in females than male rats with T2D. The decrease in adiposity index was also higher (11 % vs. 9 %, P = 0.0007) in females. SIGNIFICANCE: The anti-obesity and anti-diabetic effects of Cit in rats are sex-dependent, with Cit being more effective in female than male rats.