Citrulline counteracts overweight- and aging-related effects on adiponectin and leptin gene expression in rat white adipose tissue

• HFD and aging increase leptin mRNA and decrease adiponectin mRNA in rat adipose tissue.
• In old rats a CIT diet reduces leptin mRNA and augments adiponectin mRNA.
• In adipose tissue explants, CIT induces adiponectin mRNA whatever age and diet.
• CIT exposure of adipose tissue explants reduces leptin mRNA selectively in old rats.

We recently demonstrated that citrulline (CIT) reduced the expression of inflammatory genes in cultured explants from retroperitoneal (RET) white adipose tissue (WAT) from young (2–4 months) but not old (25 months) rats. Here we show that in RET WAT from old rats and high-fat-diet-fed (HFD) young rats, the basal expression of the leptin gene was increased (275–345%) whereas that of the adiponectin gene was decreased (48–60%), when compared to those from control-diet-fed (CD) young rats. We show also that in RET WAT from old rats, a diet supplemented with CIT for 3 months reduced macrophage (F4/80, CD68) and inflammation (interleukin-6, tumor necrosis factor-α) marker genes 23–97%. CIT supplementation lowered leptin mRNA 62% and increased adiponectin mRNA 232%. In cultured explants of RET WAT from 4 month-old CD, 4 month-old HFD and 25-month-old CD rats, the exposure to 2.5 mmol/L CIT for 24 h up-regulated adiponectin gene expression 151%, 362% and 216% respectively. In contrast, leptin gene expression was down-regulated 66% selectively in CIT-treated explants from 25-month-old CD rats. These results further support the proposed beneficial effect of CIT to counteract the deleterious effects of aging and overweight on the metabolic, inflammatory and endocrine functions of WAT.