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Surgery and brain opioids

Study finds bariatric surgery normalises brain opioids

The these findings show that the endogenous opioid system plays an important role in the pathophysiology of human obesity

Researchers at Aalto University and University of Turku, Finland, have revealed how bariatric surgery recovers opioid neurotransmission in the brain. They discovered that surgery and concomitant weight loss normalised the brain's opioid neurotransmission, which is involved in generating pleasurable sensations. The research also showed that surgery normalised brain circuits triggering pleasurable sensations when eating. The research, ‘Weight loss after bariatric surgery normalizes brain opioid receptors in morbid obesity,’ was published in the journal Molecular Psychiatry.

Lauri Nummenmaa

"Our findings highlight how obesity is associated with brain-level molecular changes, and how weight loss influences appetite control at the molecular level in the brain,” said Professor Lauri Nummenmaa from Aalto University. “It is possible that the lack of brain's opioid receptors predisposes the obese individuals to overeating to compensate decreased hedonic responses in this system. Obesity surgery however recovers this bias in the brain."

The researchers measured brain μ-opioid receptor (MOR) and dopamine D2 receptor (D2R) availability in 16 morbidly obese women twice, before and six months after bariatric surgery, using PET with [11C] carfentanil and [11C] raclopride. The data were then compared with those from 14 lean control subjects.

Obesity is associated with lowered opioid receptor availability (top row) whereas availability of dopamine receptors is unchanged. Bariatric surgery recovers the opioid system but does not influence the dopamine system

Receptor-binding potentials (BPND) were compared between the groups and between the pre- and post-operative scans among the obese subjects. Brain MOR availability was initially lower among obese subjects, but weight loss (mean=26.1kg -/+7.6 kg) reversed this and resulted in ~23% higher MOR availability in the postoperative versus preoperative scan. Changes were observed in areas implicated in reward processing, including ventral striatum, insula, amygdala and thalamus (all p<0.005).  Weight loss did not influence D2R availability in any brain region.

Henry Karlsson

"Because brain's opioid system recovers following weight loss, it is likely that their lower levels in the obese are due to weight gain,” said researcher Henry Karlsson from Turku PET Centre. “Altered neurotransmitter levels are thus a consequence rather than a cause of obesity. These results help us to understand the mechanisms involved in weight loss and appetite, and provide new insight into behavioural and pharmacological treatment.”

The researchers said that these findings show that the endogenous opioid system plays an important role in the pathophysiology of human obesity. As bariatric surgery and concomitant weight loss recover downregulated MOR availability, lowered MOR availability is associated with an obese phenotype and may mediate excessive energy uptake. The results highlight that understanding the opioidergic contribution to overeating is critical for developing new treatments for obesity.

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