title: Hypothalamic deep brain stimulation reduces weight gain in an obesity-animal model.
abstract: Prior studies of appetite regulatory networks, primarily in rodents, have established that targeted electrical stimulation of ventromedial hypothalamus (VMH) can alter food intake patterns and metabolic homeostasis. Consideration of this method for weight modulation in humans with severe overeating disorders and morbid obesity can be further advanced by modeling procedures and assessing endpoints that can provide preclinical data on efficacy and safety. In this study we adapted human deep brain stimulation (DBS) stereotactic methods and instrumentation to demonstrate in a large animal model the modulation of weight gain with VMH-DBS. Female Göttingen minipigs were used because of their dietary habits, physiologic characteristics, and brain structures that resemble those of primates. Further, these animals become obese on extra-feeding regimens. DBS electrodes were first bilaterally implanted into the VMH of the animals (n = 8) which were then maintained on a restricted food regimen for 1 mo following the surgery. The daily amount of food was then doubled for the next 2 mo in all animals to produce obesity associated with extra calorie intake, with half of the animals (n = 4) concurrently receiving continuous low frequency (50 Hz) VMH-DBS. Adverse motoric or behavioral effects were not observed subsequent to the surgical procedure or during the DBS period. Throughout this 2 mo DBS period, all animals consumed the doubled amount of daily food. However, the animals that had received VMH-DBS showed a cumulative weight gain (6.1±0.4 kg; mean ± SEM) that was lower than the nonstimulated VMH-DBS animals (9.4±1.3 kg; p<0.05), suggestive of a DBS-associated increase in metabolic rate. These results in a porcine obesity model demonstrate the efficacy and behavioral safety of a low frequency VMH-DBS application as a potential clinical strategy for modulation of body weight.
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America. wmelega@mednet.ucla.edu
authors.forename: William P
authors.initials: WP
authors.lastname: Melega
authors.forename: Goran
authors.initials: G
authors.lastname: Lacan
authors.forename: Alessandra A
authors.initials: AA
authors.lastname: Gorgulho
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Behnke
authors.forename: Antonio A F
authors.initials: AA
authors.lastname: De Salles
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001786:Blood Glucose / Q000378:metabolism; D046690:Deep Brain Stimulation / Q000379:methods*; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007031:Hypothalamus; D008279:Magnetic Resonance Imaging; D009765:Obesity / Q000097:blood / Q000503:physiopathology* / Q000601:surgery / Q000628:therapy*; D015203:Reproducibility of Results; D013552:Swine; D015430:Weight Gain
chemical_list: D001786:Blood Glucose