Molecular Psychiatry , (13 October 2015) | doi:10.1038/mp.2015.153
H K Karlsson, J J Tuulari, L Tuominen, J Hirvonen, H Honka, R Parkkola, S Helin, P Salminen, P Nuutila and L Nummenmaa
Abstract
Positron emission tomography (PET) studies suggest opioidergic system dysfunction in morbid obesity, while evidence for the role of the dopaminergic system is less consistent. Whether opioid dysfunction represents a state or trait in obesity remains unresolved, but could be assessed in obese subjects undergoing weight loss.
Here we measured brain μ-opioid receptor (MOR) and dopamine D2 receptor (D2R) availability in 16 morbidly obese women twice—before and 6 months after bariatric surgery—using PET with [11C]carfentanil and [11C]raclopride.
Data were compared with those from 14 lean control subjects. Receptor-binding potentials (BPND) were compared between the groups and between the pre- and postoperative scans among the obese subjects. Brain MOR availability was initially lower among obese subjects, but weight loss (mean=26.1 kg, s.d.=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 (P’s<0.005).
Weight loss did not influence D2R availability in any brain region.
Taken together, the endogenous opioid system plays an important role in the pathophysiology of human obesity.
Because 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. Our results highlight that understanding the opioidergic contribution to overeating is critical for developing new treatments for obesity.
Obesity surgery normalizes brain opioids
October 13, 2015
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. <
Researchers at Aalto University and University of Turku have revealed how obesity surgery recovers opioid neurotransmission in the brain.
Finnish researchers found that obesity surgery and concomitant weight loss normalized brain’s opioid neurotransmission, which is involved in generating pleasurable sensations. Obesity surgery provides an effective means for rapid weight loss, and the research also shows that obesity surgery also normalizes brain circuits triggering pleasurable sensations when eating. The research outcome was recently published in Molecular Psychiatry journal.
“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. 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,” says Professor Lauri Nummenmaa from Aalto University.
“Because brain’s opioid system recovers following weight loss, it is likely that their lower levels in the obese are due to weight gain. 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,” says researcher Henry Karlsson from Turku PET Centre.
Obesity is a great challenge to human health worldwide because it is associated with serious medical conditions such as type 2 diabetes, coronary heart disease, and stroke. Obesity is also associated with alterations in the brain circuits that generate pleasurable sensations when eating, thus predisposing individuals to overeating.
The researchers measured availability of mu-opioid and type 2 dopamine receptors in normal-weight and obese individuals’ brains using positron emission tomography at the Turku PET Centre. The obese subjects underwent bariatric surgery, after which their brains were scanned again.
Explore further: Obesity is associated with altered brain function
More information: H K Karlsson et al. “Weight loss after bariatric surgery normalizes brain opioid receptors in morbid obesity,” Molecular Psychiatry (2015). DOI: 10.1038/mp.2015.153
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