Brain opioid and endocannabinoid systems as risk factors for obesity. Positron emission tomography studies of μ-opioid and CB1 receptors with glucose uptake analysis
Year: 2022
Type: dissertation
Study design: Observational Study
Abstract: The prevalence of obesity is increasing globally. Obesity is a major threat to public health since it predisposes individuals to multiple non-communicable diseases. Obesity is difficult to treat or prevent. The modern environment has been blamed for the obesity epidemic, due to the abundance of energy-dense and aggressively advertised foods. The brain is the most important organ controlling energy homeostasis and feeding. However, we do not know which brain pathways render some individuals susceptible to the obesity development in the current environment. The aim of this thesis was to examine whether variation in the brain opioid and endocannabinoid pathways explains differences in the risk for obesity development. Two receptor systems associated with food intake and reward processing were investigated: μ-opioid receptors (MOR) and cannabinoid CB1 receptors (CB1R). MORs were measured with [11C]carfentanil, and CB1Rs with [18F]FMPEP-d2. In addition, brain glucose uptake (BGU) was quantified with [18F]FDG. Healthy, non-obese humans were studied with positron emission tomography in four studies investigating I) the effects of demographic factors on MORs, II) the associations of obesity risk factors on MORs, CB1Rs and BGU, III) the physical fitness and MOR function, and IV) how MORs and CB1Rs associate with feeding behavior. Age, sex and smoking influenced MOR availability, which may contribute to obesity development in specific populations. Familial obesity risk associated with increased BGU but low neuroreceptor availability, suggesting that vulnerability to obesity may be mediated by disruption of these interconnected pathways. Impulsive feeding was associated with reduced MOR availability, which may underlie excessive food intake and weight gain. Central capacity for releasing endogenous MOR ligands was dependent on aerobic fitness, suggesting that the MOR function may be critical in habitual exercise and weight maintenance. Obesity risk factors and circulating cannabinoids associated with reduced CB1R availability, suggesting that an overactive cannabinoid system may facilitate weight gain. In conclusion, multiple neurochemical alterations previously associated with obesity are already present in a number of non-obese individuals, which may increase their risk for future obesity.
Source: UTUPub (University of Turku)
Author: Kantonen, Tatu
Language: English
Subfield: Pharmacology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7064458949