Gastric electrical stimulation parameter dependently alters ventral medial hypothalamic activity and feeding in obese rats

Abstract

. Gastric electrical stimulation parameter dependently alters ventral medial hypothalamic activity and feeding in obese rats. Am J Physiol Gastrointest Liver Physiol 301: G912-G918, 2011. First published August 18, 2011 doi:10.1152/ajpgi.00487.2010.-Gastric electrical stimulation (GES) has been used to treat obesity with unclear mechanisms and limited parameter ranges. This study explores effects of GES parameters on ventral medial hypothalamic (VMH) activity, feeding, and body weight in diet-induced obese (DIO) rats. For experiment 1, discharge rates were recorded in 39 gastric distension-responsive (GD-R) neurons in 12 DIO rats. Basal rates were compared with rates under GES using varied pulse amplitudes, widths, frequencies, and train-on times. For experiment 2, a crossover experiment in 16 DIO rats measured food intake and weight effects of GES pulse width, the parameter with the steepest neuronal response gradient in experiment 1. Treatments were sham and 0.5-, 2.0-, and 5.0-ms pulse GES. In experiment 1, 11 of 13 GES parameter sets tested produced significantly (P Ͻ 0.05) altered discharge rates of GD-R neurons. Increases in pulse amplitude (P Ͻ 0.05) and width (P Ͻ 0.0001) produced significant upward linear trends in response over the range tested, with the trend being strongest for pulse width. In experiment 2, over 4 days of 0.5-, 2.0-, and 5.0-ms GES treatment, food intake was 9.6% (P Ͻ 0.05), 21.0% (P Ͻ 0.0001), and 47.3% (P Ͻ 0.0001) lower than under sham-GES, whereas body weight changes were 0.7 (P ϭ 0.48), 2.2 (P Ͻ 0.05), and 3.5 (P Ͻ 0.002) percentage points lower, respectively. We concluded that GES pulse width increases had the largest effect on VMH neuronal activity, and these effects were paralleled by pulse width-dependent reductions in food intake and body weight. Lengthening pulse width beyond the range used in prior clinical studies may be critical to making GES a viable obesity treatment. ventromedial hypothalamus; gastric distension; food intake; obesity THE PREVALENCE OF OBESITY is rising worldwide, and the majority of adults in the United States and many developed countries are overweight or obese. It is estimated that 1.6 billion adults worldwide are overweight [body mass index (BMI) Ͼ 25] and 400 million are obese (BMI Ͼ 30) (1). Obesity and its comorbidities have been estimated to claim over 400,000 lives and cost over $100 billion annually in the US alone (11). Obesity is associated with higher rates of disability and all-cause mortality, and the obese have increased incidences of type 2 diabetes, cardiovascular disease, musculoskeletal disorders, sleep apnea, fatty liver disease, and certain cancers.Conventional obesity treatments fall into three categories: behavioral treatments focused on diet and exercise, pharmacotherapy, and surgical treatments. Although many patients achieve weight loss through behavioral treatments, only a small minority succeed in maintaining their losses. Similarly, Food and Drug Administration-approved antiobesity drugs have demonstrated only short-term...

Pulse Width-Dependent Effects of Intestinal Electrical Stimulation for Obesity: Role of Gastrointestinal Motility and Hormones

“…GLP-1 is an insulinotropic hormone which has been shown to inhibit food intake and induce weight loss in humans [27,28]. Both the peripheral effect on gastric emptying [27] and the central effect on appetite regulation [10,11] contribute to the anorectic effect of GLP-1. In the present study, we investigated the effect of IES with varied pulse width on the secretion of GLP-1 stimulated by oral glucose.…”

“…However, randomized placebo-controlled clinical studies did not yield significant weight loss effects on obese patients [8]. Due to the limitations of the available implantable stimulators, GES for treating obesity patients was confined to a narrow range of stimulation parameters with pulse width below 1 ms, despite several animal studies indicating that wider pulse widths are more effective in modulating gastric motility, reduce food intake, and body weight [9,10].…”

Parameter Selection and Stimulating Effects of an Adjustable Gastric Electrical Stimulator in Dogs

“…Recently, more experiments have proved the importance of pulse width in the stimulation process [28–30]. The possible mechanisms between expanded pulse width and reduced food intake or body weight have not been fully elucidated.…”

Chronic Electrical Stimulation at Acupoints Reduces Body Weight and Improves Blood Glucose in Obese Rats via Autonomic Pathway

“…Sixteen DIO rats were acclimated to 2-h daily food intake in restrainers until they were able to consume the full amount of food for a day within the 2-h period [6,7]. Once acclimated, four sets of different parameters were used in a randomized order with each treatment lasting for 1 week.…”