A single injection of the GLP-1 receptor agonist liraglutide led to short-term normalization of associative studying in individuals with obesity and insulin resistance, a discovering that implies dopamine-driven studying processes are modified by metabolic signaling and that this impact “might contribute to the weight-reducing results of liraglutide in weight problems,” say the authors of a recent report in Nature Metabolism.
“We demonstrated that dopamine-driven associative studying about exterior sensory cues crucially will depend on metabolic signaling,” mentioned Marc Tittgemeyer, PhD, professor on the Max Planck Institute for Metabolism Analysis in Cologne, Germany, and senior writer of the research. Examine contributors with impaired insulin sensitivity “exhibited a lowered amplitude of behavioral updating that was normalized” by a single subcutaneous injection of 0.6 mg of liraglutide (the beginning day by day dose for liraglutide for weight reduction, obtainable as Saxenda, Novo Nordisk) given the night earlier than testing.
The findings, from 30 adults with regular insulin sensitivity and regular weight and 24 adults with impaired insulin sensitivity and weight problems, counsel that metabolic indicators, notably ones that promote power restoration in a setting of power deprivation brought on by insulin or a glucagon-like peptide-1 (GLP-1) receptor agonist, “profoundly affect neuronal processing,” mentioned Tittgemeyer. The findings counsel that impaired metabolic signaling akin to happens with insulin resistance in individuals with weight problems could cause deficiencies in associative studying.
“Liraglutide Can Normalize Studying of Associations”
“We present that in individuals with weight problems, disrupted circuit mechanisms result in impaired studying about sensory associations,” Tittgemeyer mentioned in an interview. “The data supplied by sensory programs that the mind should interpret to pick a behavioral response are ‘off tune'” in these people.
“That is reasonably consequential for understanding food-intake behaviors. Trendy weight problems therapies, akin to liraglutide, can normalize studying of associations and thereby render individuals inclined once more for sensory indicators and make them extra vulnerable to react to subliminal interactions, akin to weight-normalizing diets and acutely aware consuming,” he added.
The normalization in associative studying that one dose of liraglutide produced in individuals with weight problems “matches with research displaying that these medicine restore a standard feeling of satiety, inflicting individuals to eat much less and due to this fact reduce weight,” he defined.
Tittgemeyer famous that this impact is probably going shared by different brokers within the GLP-1 receptor agonist class, akin to semaglutide (Ozempic, Wegovy, Novo Nordisk) however is probably going not an impact when brokers agonize receptors to different nutrient-stimulated hormones akin to glucagon and the glucose-dependent insulinotropic polypeptide (GIP).
The findings “present that liraglutide restores associative studying in contributors with better insulin resistance,” a “extremely related” discovery, commented Nils B. Kroemer, PhD, head of the Part of Medical Psychology on the College of Bonn, Germany, who was not concerned with this analysis, in a written assertion.
The research run by Tittgemeyer and his associates included 54 wholesome grownup volunteers whom they assessed for insulin sensitivity with their homeostasis mannequin evaluation of insulin resistance. The researchers divided the cohort into teams; one group included 24 individuals with impaired insulin sensitivity, and one included 30 with regular insulin sensitivity. The common physique mass index (BMI) of the traditional sensitivity group was about 24 kg/m2; within the insulin-resistant subgroup, BMI averaged about 33 kg/m2.
The associative studying activity examined the flexibility of contributors to study associations between auditory cues (a excessive or low tone) and a subsequent visible final result (an image of a face or a home). Throughout every associative studying session, contributors additionally underwent practical MRI of the mind.
Liraglutide Therapy Leveled Studying
The outcomes confirmed that the training fee was considerably decrease within the subgroup with impaired insulin sensitivity in contrast with these with regular insulin sensitivity following therapy with a placebo injection. This means a decreased adaptation of studying to predictability variations in people with impaired insulin sensitivity.
In distinction, therapy with a single dose of liraglutide considerably enhanced the training fee within the group with impaired insulin sensitivity however considerably lowered the training fee within the group with regular insulin sensitivity. Liraglutide’s impact was twice as giant within the group with impaired insulin sensitivity than within the group with regular insulin sensitivity, and these opposing results of liraglutide resulted in a convergence of the 2 teams’ adaptive studying charges in order that there wasn’t any vital between-group distinction following liraglutide therapy.
After analyzing the practical MRI information together with the training outcomes, the researchers concluded that liraglutide normalized studying in people with impaired insulin sensitivity by enhancing adaptive prediction error encoding within the mind’s ventral striatum and mesocortical projection websites.
This obvious skill of GLP-1 analogues to appropriate this studying deficit in individuals with impaired insulin sensitivity and weight problems has implications relating to potential profit for individuals with different pathologies characterised by impaired dopaminergic perform and related to metabolic impairments, akin to psychosis, Parkinson’s disease, and depression, the researchers say.
“The fascinating factor about GLP-1 receptor agonists is that they’ve an extra mechanism that pertains to anti-inflammatory results, particularly for assuaging cell stress,” mentioned Tittgemeyer. “Many ongoing scientific trials are assessing their results in neuropsychiatric ailments,” he famous.
The research acquired no industrial funding. Tittgemyer and most of his co-authors had no disclosures. One co-author had a number of disclosures, that are detailed within the report. Kroemer had no disclosures.
Nat Metab. Revealed August 17, 2023. Full text
Mitchel L. Zoler is a reporter with Medscape and MDedge based mostly within the Philadelphia area. @mitchelzoler