Background: Obesity is a complex disease that is not entirely new, but what is new is how many people develop obesity. Stimulation of brown adipose tissue (BAT) and browning of white adipose tissue (bWAT) have shown promise as therapeutic targets to increase energy expenditure and counteract weight gain. Objectives: This study aimed to examine two main aspects. Firstly, we examined how obesity impacts the expression of FNDC5 and UCP1 genes in male Wistar rats. Secondly, we investigated the effects of six weeks of aerobic exercises, exposure to cold water, and the combination of both on the FNDC5 and UCP1 genes in obese male Wistar rats. Methods: In this experiment, 25 male Wistar rats were randomly assigned to five groups (with 5 rats in each group) after inducing obesity. The groups included a control group (C), an obesity group (O), an obesity group exposed to cold water (OC), an obesity group engaged in aerobic exercise (OE), and an obesity group exposed to both cold water and aerobic exercise (OCE). The aerobic exercise sessions lasted for 30-60 minutes, with a speed of 15-25 meters per minute. The cold water exposure protocol involved shallow water (2-4 cm) with a temperature of 14-18°C. The OCE group performed both aerobic and cold water exercises in each session. The expression of the FNDC5 gene in the soleus muscle and the FNDC5 and UCP1 gene in subcutaneous fat was evaluated using Real-Time-PCR. All statistical analyses were conducted using SPSS software version 16, with a significance level set at P ≤ 0.05. Results: Obesity had a notable impact on elevating the expression of the FNDC5 gene (P=0.008). However, after six weeks of aerobic exercise (P=0.016) or exposure to cold water (P=0.016), there was a significant decrease in its expression. Surprisingly, the combination of both interventions did not result in a significant effect (P=0.75). On the other hand, none of the interventions targeting obesity, including six weeks of aerobic exercise, exposure to cold water, or their combination, had a significant effect on the expression of the UCP1 gene (P>0.05). Conclusions: The elevation in FNDC5 gene expression caused by obesity may serve as a compensatory mechanism to cope with obesity. However, it appears that both cold water exposure and aerobic exercise through increased thermogenesis can mitigate this increase in FNDC5 gene expression.

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