Gastric electrical stimulation for obesity: the need for a new device using wider pulses

Gastric electrical stimulation (GES) has been proposed as a therapeutic option for obesity. However, its clinical efficacy is not proven, and its mechanisms remain largely unknown. To compare the peripheral and central neural and behavioral effects in rats of GES with a pulse width currently used in clinical trials (GES-A: 6 mA, 0.3 ms, 40 Hz, 2 s on, 3 s off) and GES with a wider pulse (GES-B: same as GES-A, except that the pulse width is 3 ms). Experiment 1: assessing gastric volume changes as a result of GES. Experiment 2: recording the extracellular potentials of a single neuron in the paraventricular nucleus (PVN) with GES. Experiment 3: determining the effects of GES on oxytocin-immunoreactive (OT-IR) neuron expression in the hypothalamus. Experiment 4: determining the effects of GES on food intake and body weight. GES-B, but not GES-A, significantly increased gastric volume. GES-B activated a higher percentage of gastric distention-responsive neurons in the PVN (93% vs. 81%, P = 0.021) and elicited more intensive neuronal responses than GES-A. The number of OT-IR neurons was significantly increased in the PVN and supraoptic nucleus with both methods of GES compared with control groups. The increase in OT-IR neurons in the PVN was higher with GES-B than with GES-A. A 1-week GES treatment significantly reduced daily food intake and body weight. GES-B was more potent than GES-A in producing weight loss (P < 0.001). The effects of GES depend on the stimulation pulse width. GES with a wider pulse is more effective both peripherally and centrally and more potent in reducing body weight in rats.