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Abstract: Chronic vagus nerve stimulation (VNS) is known to influence food intake and body weight in animals and humans. The aim of our work was to evaluate the effects of long-term VNS in adult obese minipigs. Eight minipigs were fed ad libitum a Western diet to cause obesity, after which half of the animals were implanted with bilateral vagal electrodes connected to constant current stimulators (2mA, 30Hz, 500-μs pulse, ON 30s, OFF 5min). The other animals were implanted with sham devices. Animals were weighed weekly and their daily consumption was measured. Still 14 weeks after surgery, VNS animals (70.3±3.3kg, P >0.10) did not significantly gain weight compared to sham animals (80.6±8.0kg, P <0.05). Furthermore, food consumption decreased in VNS animals (−18%, P <0.02) compared to sham animals (+1%, P >0.10). When subjected to a three-choice meal test (high-fat vs. high-carbohydrates vs. balanced diet), VNS animals decreased their sweet-food consumption compared to sham animals (P <0.05), and increased their balanced diet consumption in comparison to pre-surgery levels. Our results showed that chronic VNS decreased weight gain, food consumption and sweet craving in adult obese minipigs, which indicates that this therapy might be used to decrease appetite in the context of morbid obesity. [Copyright &y& Elsevier]