The Role of the Noradrenergic System in Eating Disorders: A Systematic Review

Pruccoli, Jacopo; Parmeggiani, Antonia; Cordelli, Duccio Maria; Lanari, Marcello

doi:10.3390/ijms222011086

Cited by 13 publications

(14 citation statements)

References 79 publications

(118 reference statements)

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“…The mechanism of action of phentermine is not fully understood; however, it is known that phentermine induces norepinephrine (NE) and dopamine release by inhibiting its recapture in the hypothalamus [ 32 , 33 ]. In the rat model, NE injection into the hypothalamus was found to reduce food consumption, while NE depletion caused by ascending ventral NE axon lesions led to overeating, thus suggesting that NE promotes satiety [ 34 , 35 ]. However, other studies suggest an opposite effect of exogenous NE in the hypothalamus, decreasing satiety in rats [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions

Salazar-Valencia

Villamil‐Ramírez

Barajas‐Olmos

et al. 2022

Genes

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The loss of function melanocortin 4-receptor (MC4R) Ile269Asn mutation has been proposed as one of the most important genetic contributors to obesity in the Mexican population. However, whether patients bearing this mutation respond differently to weight loss treatments is unknown. We tested the association of this mutation with obesity in 1683 Mexican adults, and compared the response of mutation carriers and non-carriers to three different weight loss interventions: dietary restriction intervention, phentermine 30 mg/day treatment, and Roux-en-Y gastric bypass (RYGB) surgery. The Ile269Asn mutation was associated with obesity [OR = 3.8, 95% CI (1.5–9.7), p = 0.005]. Regarding interventions, in the dietary restriction group only two patients were MC4R Ile269Asn mutation carriers. After 1 month of treatment, both mutation carriers lost weight: −4.0 kg (−2.9%) in patient 1, and −1.8 kg (−1.5%) in patient 2; similar to the mean weight loss observed in six non-carrier subjects (−2.9 kg; −2.8%). Phentermine treatment produced similar weight loss in six carriers (−12.7 kg; 15.5%) and 18 non-carriers (−11.3 kg; 13.6%) after 6 months of pharmacological treatment. RYGB also caused similar weight loss in seven carriers (29.9%) and 24 non-carriers (27.8%), 6 months after surgery. Our findings suggest that while the presence of a single MC4R loss of function Ile269Asn allele significantly increases obesity risk, the presence of at least one functional MC4R allele seems sufficient to allow short-term weight loss in response to dietary restriction, phentermine and RYGB. Thus, these three different interventions may be useful for the short-term treatment of obesity in MC4R Ile269Asn mutation carriers.

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Section: Discussionmentioning

confidence: 99%

Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions

Salazar-Valencia

Villamil‐Ramírez

Barajas‐Olmos

et al. 2022

Genes

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“…A recent systematic review identified a series of key data on the relationship between the noradrenergic system and EDs. Besides its relevant direct, hypothalamus-based actions on feeding regulation, the noradrenergic system is indirectly implied in various endocrine networks controlling human nutrition [64]. Dopamine is a neurotransmitter that regulates the rewarding nature of food [65].…”

Section: Biochemicalmentioning

confidence: 99%

Obesity and Eating Disorders in Children and Adolescents: The Bidirectional Link

et al. 2021

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Obesity, eating disorders and unhealthy dieting practices among children and adolescents are alarming health concerns due to their high prevalence and adverse effects on physical and psychosocial health. We present the evidence that eating disorders and obesity can be managed or prevented using the same interventions in the pediatric age. In the presence of obesity in the pediatric age, disordered eating behaviors are highly prevalent, increasing the risk of developing eating disorders. The most frequently observed in subjects with obesity are bulimia nervosa and binge-eating disorders, both of which are characterized by abnormal eating or weight-control behaviors. Various are the mechanisms overlying the interaction including environmental and individual ones, and different are the approaches to reduce the consequences. Evidence-based treatments for obesity and eating disorders in childhood include as first line approaches weight loss with nutritional management and lifestyle modification via behavioral psychotherapy, as well as treatment of psychiatric comorbidities if those are not a consequence of the eating disorder. Drugs and bariatric surgery need to be used in extreme cases. Future research is necessary for early detection of risk factors for prevention, more precise elucidation of the mechanisms that underpin these problems and, finally, in the cases requiring therapeutic intervention, to provide tailored and timely treatment. Collective efforts between the fields are crucial for reducing the factors of health disparity and improving public health.

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“…Our observed effects from the dietary conditions were more pronounced with the use of selective norepinephrine or dopamine reuptake inhibitors. Alterations in the noradrenergic system have been implicated in binge eating pathologies (Pruccoli et al ., 2021). One of our major findings of this study was that a high dose of nisoxetine (5 mg/kg) resulted in a diminished response to the startle pulse (110 dB) in the RB group compared with the control (N) group under standard chow conditions.…”

Section: Discussionmentioning

confidence: 99%

Dietary-induced binge-like eating impairs acoustic startle responses to acute nisoxetine in male mice

Scarpa

Bello

2023

Behavioural Pharmacology

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Sensorimotor gating disruptions have been noted in several psychiatric and neurodegenerative disorders. However, the involvement of sensorimotor gating processes in eating disorders has not been well characterized. Our objective was to examine the sensorimotor gating of the acoustic startle response following dietary-induced binge eating and high-fat diet (HFD) induced weight gain in male C57B/6J mice. Acute administration of the norepinephrine reuptake inhibitor, nisoxetine (0.5 and 5 mg/kg), and a dopamine reuptake inhibitor, GBR 12783 (1.6 and 16 mg/kg), were either given alone or in combination to assess norepinephrine and dopamine alterations, respectively. Male mice with repeated bouts of calorie restriction (Restrict) and with limited access to a sweetened fat food (Binge) demonstrated an escalation of intake over 2.5 weeks under standard chow conditions. Restrict Binge (RB) mice had a reduced startle response to the startle pulse (110 dB) compared with the Naive control group at 5 mg/kg nisoxetine. There was an overall effect of nisoxetine (0.5 and 5 mg/kg) to increase percent inhibition at pre-pulse (74 dB), %PP74. Under HFD conditions, the RB group did not demonstrate a binge-like eating phenotype. The RB group on HFD had a higher response to 74 dB with nisoxetine (5.0 mg/kg) compared with a combinational dose of nisoxetine (5.0 mg/kg) and GBR 12783 (1.6 mg/kg). These findings suggest that dietary conditions that promote binge-like eating can influence the central noradrenergic and dopaminergic controls of the acoustic startle response and potentially influence sensorimotor gating.

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The Role of the Noradrenergic System in Eating Disorders: A Systematic Review

Cited by 13 publications

References 79 publications

Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions

Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions

Obesity and Eating Disorders in Children and Adolescents: The Bidirectional Link

Dietary-induced binge-like eating impairs acoustic startle responses to acute nisoxetine in male mice

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