GLP-1 and hunger modulate incentive motivation depending on insulin sensitivity in humans

Hanßen, Ruth; Kretschmer, Alina Chloé; Rigoux, Lionel; Albus, Kerstin; Thanarajah, Sharmili Edwin; Sitnikow, Tamara; Melzer, Corina; Cornely, Oliver A.; Tittgemeyer, Marc

doi:10.1016/j.molmet.2021.101163

Cited by 26 publications

(19 citation statements)

References 93 publications

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“…We could show that hunger increases incentive motivation in lean humans but not in obese humans indicating that motivational irregularities in obesity are state-dependent. We further observed that the effect of hun ger on incentive motivation is modulated by the peripheral insulin sensitivity of the individual with impaired peripheral insulin sensi tivity reducing the motivational effect of hunger [64]. These results are in line with previous studies showing that altered insulin sensi tivity impacts dopaminergic projections of the midbrain and de note a dysfunctional integration of metabolic signals and external cues within the mesolimbic system as the foundation of impaired motivational drive in obesity [65].…”

Section: Metabolic Modulation Of Motivational Behavior In Humans and ...supporting

confidence: 91%

“…We further demonstrate that administration of the GLP-1 analogue liraglutide normalizes the motivational effect of hunger in insulin-resistant humans. Most importantly, this holds true for both food and monetary reward, indicating that the modulatory effect of GLP-1 on motivational behavior exceeds a mere food scenario and might prove beneficial in other disorders with motivational deficits 64 .…”

Section: Metabolic Modulation Of Motivational Behavior In Humans and ...mentioning

confidence: 98%

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Obesity – A Matter of Motivation?

Hanßen

Thanarajah

Tittgemeyer

2022

Exp Clin Endocrinol Diabetes

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Excessive food intake and reduced physical activity have long been established as primary causes of obesity. However, the underlying mechanisms causing this unhealthy behavior characterized by heightened motivation for food but not for physical effort are unclear. Despite the common unjustified stigmatization that obesity is a result of laziness and lack of discipline, it is becoming increasingly clear that high-fat diet feeding and obesity cause alterations in brain circuits that are critical for the control of motivational behavior.In this mini-review, we provide a comprehensive overview of incentive motivation, its neural encoding in the dopaminergic mesolimbic system as well as its metabolic modulation with a focus on derangements of incentive motivation in obesity. We further discuss the emerging field of metabolic interventions to counteract motivational deficits and their potential clinical implications.

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Section: Metabolic Modulation Of Motivational Behavior In Humans and ...supporting

confidence: 91%

Section: Metabolic Modulation Of Motivational Behavior In Humans and ...mentioning

confidence: 98%

Obesity – A Matter of Motivation?

Hanßen

Thanarajah

Tittgemeyer

2022

Exp Clin Endocrinol Diabetes

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“…GLP-1 s influence on food-motivated behaviors in human participants can be impaired by metabolic conditions. For example, in an incentive motivation task where participants exert physical strength on a handgrip to obtain food or monetary rewards, sc injection of the GLP-1 analog liraglutide prevents the increase in incentive motivation induced by hunger in participants with high, but not low, insulin sensitivity [97]. Interestingly, RYGB surgery reduces computer mouse clicks for a sweet and fatty candy [98] and this may be related to improvements in GLP-1 signaling.…”

Section: Human Studiesmentioning

confidence: 99%

Ghrelin and Glucagon-Like Peptide-1: A Gut-Brain Axis Battle for Food Reward

Décarie-Spain

Kanoski

2021

Nutrients

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Eating behaviors are influenced by the reinforcing properties of foods that can favor decisions driven by reward incentives over metabolic needs. These food reward-motivated behaviors are modulated by gut-derived peptides such as ghrelin and glucagon-like peptide-1 (GLP-1) that are well-established to promote or reduce energy intake, respectively. In this review we highlight the antagonizing actions of ghrelin and GLP-1 on various behavioral constructs related to food reward/reinforcement, including reactivity to food cues, conditioned meal anticipation, effort-based food-motivated behaviors, and flavor-nutrient preference and aversion learning. We integrate physiological and behavioral neuroscience studies conducted in both rodents and human to illustrate translational findings of interest for the treatment of obesity or metabolic impairments. Collectively, the literature discussed herein highlights a model where ghrelin and GLP-1 regulate food reward-motivated behaviors via both competing and independent neurobiological and behavioral mechanisms.

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“…[8] also showed that liraglutide may increase the right orbitofrontal cortex response to food cues when administrated at a high dose and in a long-term fashion. More recently, Hanssen et al [9] have shown behavioral evidence of GLP-1 modulation of incentive motivation on food rewards but did not investigate neural correlates of this effect.…”

Section: Introductionmentioning

confidence: 99%

Does GLP-1 receptor agonist liraglutide alter food-related sensory pleasure in patients with obesity? A randomized controlled trial

Coppin,

David,

Pool

et al. 2022

Preprint

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Background/Objectives: Obesity is a complex condition and the mechanisms involved in weight gain and loss are poorly understood. Liraglutide, a GLP-1 receptor agonist, has been demonstrated to successfully promote weight loss in patients with obesity (OB). Yet, it is unclear whether the observed weight loss is driven by an alteration of food reward processing. Here we investigated the effects of liraglutide on cerebral correlates of food-related sensory pleasure in OB. Subjects/Methods: This study was a randomized, single-centre, double-blind, placebo-controlled, parallel group, prospective clinical trial. 73 patients with OB and without diabetes were randomly assigned (1:1) to receive liraglutide 3.0 mg (37.40±11.18 years old, BMI = 35.89 kg ±3.01) or placebo (40.04±14.10 years old, BMI = 34.88 kg ±2.87) subcutaneously once daily, for 16 weeks. They also followed a multidisciplinary weight loss program. Interventions/Methods: We investigated sensory pleasure during food consumption (i.e., “liking”). Participants reported their hedonic experience while consuming a high-calorie food (milkshake) and a tasteless solution. The solutions were administered inside the scanner with a Magnetic Resonance Imaging (MRI)-compatible gustometer to assess neural responses during consumption. The same procedure was repeated for pre- and post-intervention sessions. Results: The liraglutide group lost more weight (BMI post-pre = - 3.19 kg/m2 ±1.28) than the placebo group (BMI post-pre = - 0.60 kg/m2 ±1.26). The sensory pleasure during food reward consumption was associated with the activation of the ventromedial prefrontal cortex (vmPFC) and the amygdala. We did not find any statistically significant difference in the liraglutide group between the pre and post sessions, neither at a subjective level nor at a neural level in terms of reactivity of the vmPFC to the milkshake.Conclusions: These results suggest that liraglutide leads to weight loss without self-report or neural evidence supporting a concomitant reduction of food-related sensory pleasure in patients with from obesity.

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GLP-1 and hunger modulate incentive motivation depending on insulin sensitivity in humans

Cited by 26 publications

References 93 publications

Obesity – A Matter of Motivation?

Obesity – A Matter of Motivation?

Ghrelin and Glucagon-Like Peptide-1: A Gut-Brain Axis Battle for Food Reward

Does GLP-1 receptor agonist liraglutide alter food-related sensory pleasure in patients with obesity? A randomized controlled trial

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