OBJECTIVE:The authors proposed an intraventricular 'floating' electrode inserted in the third ventricle (V3) adjacent to the ventromedian hypothalamus (VMH) in a freely moving Macaca fascicularis to modulate food intake (FI), body fat (BF), body weight (BW) and body mass index (BMI), as a potential treatment of obesity. METHODS: Five adult Macaca fascicularis monkeys were implanted stereotactically in the V3 contiguous to the VMH with one deep brain stimulation (DBS) electrode. The study was divided in two phases: (a) acute 24 h-fasting trials: different electrical stimulation parameters were applied to a fasting primate to determine the best combination in reducing FI; and (b) chronic 8-week stimulation trials: three cycles of intraventricular-VMH DBS lasting 8 --10 weeks were performed at 130 Hz, 80 Hz (most effective frequency reducing FI) and 30 Hz, respectively. BMI, BW, BF content, skinfolds and hormones were measured during baseline and at the end of each session of stimulation. RESULTS: Acute 24 h-fasting trials: there was a decrease in FI in all subjects at 80 Hz, (11 --19%, mean 15%). Chronic 8-week stimulation trials: a significant decrease in BW and BMI was observed in three out of four monkeys at 80 Hz (mean 8 ± 4.4%). Subcutaneous skinfolds were reduced in all four subjects at 80 Hz and slightly increased at 130 Hz. The sham monkey remained stable. No significant adverse effects were recorded. CONCLUSION: The stimulation of the VMH region through an intraventricular approach might acutely modulate FI and induce a sustained decrease in BW and fat mass in normal non-human primate.
INTRODUCTIONObesity is a complex disorder that has reached epidemic proportions globally, with more than 1 billion adults overweight, according to WHO. It is associated with diminished quality of life 1 and reduces life expectancy. 2 Treatment includes non-pharmacological measures, drugs and surgical therapy. The use of pharmacological agents has demonstrated only discreet body weight (BW) reduction in controlled trials. For the surgery, some patients with morbid obesity still remain poor candidates for standard gastric bypass: complications occur in 15 --55% of bariatric patients, and the peri-surgical mortality rate is about 1.5% even in experienced centers. 3 Safer procedures, such as laparoscopic adjustable banded gastroplasty, are simpler but are not as effective. 4,5 Large room for effective and safer procedures still exists.Recently, modulation of brain circuits has emerged as a valuable clinical and research strategy in obesity. With the development of new hardware and electrophysiological techniques, deep brain stimulation (DBS) have been used for treating movement disorder, 6 pain, 7 obsessive compulsive disorders 8 --10 and clinical refractory epilepsy. 11,12 A recent report on the hypothalamic DBS applied in cases of chronic intractable cluster headaches 13 has revived the interest in the hypothalamic region, which is also wellknown to be involved in food intake (FI) and energy balance regulation. DBS is a reve...