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

Jing Zhang, Roland Maude-Griffin, Hongbing Zhu, Yan Sun, Warren Starkebaum, Elizabeth Firestone, Jiande D.Z. Chen

Research output: Contribution to journalArticlepeer-review

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 < 0.05) altered discharge rates of GD-R neurons. Increases in pulse amplitude (P < 0.05) and width (P < 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 < 0.05), 21.0% (P < 0.0001), and 47.3% (P < 0.0001) lower than under sham-GES, whereas body weight changes were 0.7 (P = 0.48), 2.2 (P < 0.05), and 3.5 (P < 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.

Original languageEnglish (US)
Pages (from-to)G912-G918
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume301
Issue number5
DOIs
StatePublished - Nov 1 2011
Externally publishedYes

Keywords

  • Food intake
  • Gastric distension
  • Obesity
  • Ventromedial hypothalamus

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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