AgRP neurons control compulsive exercise and survival in an activity-based anorexia model

Miletta, Maria Consolata; İyilikci, Onur; Shanabrough, Marya; Šestan-Peša, Matija; Cammisa, Allison; Zeiss, Caroline J.; Dietrich, Marcelo O; Horváth, Tamas L.

doi:10.1038/s42255-020-00300-8

Cited by 51 publications

(55 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Surprisingly, POMC ARC activity is only increased after fasted exercise, suggesting these neurons may possibly mediate suppression of food intake in response to fasted HIE (Figure 7). Notably, the current study only examined neuronal changes 1-hour post-exercise, the time point immediately before changes in food intake were first observed, and changes in neuronal activity after exercise are rapid and transient (5)(6)(7). For example, it is unclear what is driving compensatory increases in food intake 6-12-hours after fasted exercise.…”

Section: Discussionmentioning

confidence: 98%

“…While the reasons for these energy status-dependent differences in feeding behavior are unclear, glucose and metabolic hormone concentrations also fluctuate with energy status, modulating activity of neuron populations involved in regulating feeding behavior (19,20,22,32). Consequently, recent studies have investigated the potential role for exercise to modulate activity of hypothalamic neurons involved in regulating appetite (3)(4)(5)(6)(7).…”

Section: Discussionmentioning

confidence: 99%

“…Identified ARC neurons modulated by acute treadmill exercise include the neuropeptide Y/agouti-related peptide (NPY/AgRP ARC ) and pro-opiomelanocortin (POMC ARC ) -expressing neuron populations (3)(4)(5)(6)(7). POMC ARC neurons suppress food intake by releasing a-melanocyte-stimulating hormone (aMSH), which binds to melanocortin 4 receptors (MC4R's) to excite satiety-inducing neurons in the paraventricular nucleus of the hypothalamus (PVN) (1,8).…”

Section: Introductionmentioning

confidence: 99%

“…Results in POMC ARC neurons are equally equivocal, with one report observing no changes in response to fasted MIE (4) and others observing increased activity after fasted high intensity exercise (HIE) (3) and fed HIIT (5). Notably, all these studies analyzed neuronal activity at a single timepoint immediately after exercise, and exercise-mediated changes in neuronal activity in the hypothalamus can be rapid and transient (5)(6)(7). The reported effects may reflect neuroendocrine responses during exercise, rather than changes after exercise, and may also miss critical changes in neuronal activity in the hours after exercise.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Energy Status Differentially Modifies Feeding Behavior and POMCARC Neuron Activity After Acute Treadmill Exercise in Untrained Mice

et al. 2021

View full text Add to dashboard Cite

Emerging evidence identifies a potent role for aerobic exercise to modulate activity of neurons involved in regulating appetite; however, these studies produce conflicting results. These discrepancies may be, in part, due to methodological differences, including differences in exercise intensity and pre-exercise energy status. Consequently, the current study utilized a translational, well-controlled, within-subject, treadmill exercise protocol to investigate the differential effects of energy status and exercise intensity on post-exercise feeding behavior and appetite-controlling neurons in the hypothalamus. Mature, untrained male mice were exposed to acute sedentary, low (10m/min), moderate (14m/min), and high (18m/min) intensity treadmill exercise in a randomized crossover design. Fed and 10-hour-fasted mice were used, and food intake was monitored 48h. post-exercise. Immunohistochemical detection of cFOS was performed 1-hour post-exercise to determine changes in hypothalamic NPY/AgRP, POMC, tyrosine hydroxylase, and SIM1-expressing neuron activity concurrent with changes in food intake. Additionally, stains for pSTAT3tyr705 and pERKthr202/tyr204 were performed to detect exercise-mediated changes in intracellular signaling. Results demonstrated that fasted high intensity exercise suppressed food intake compared to sedentary trials, which was concurrent with increased anorexigenic POMC neuron activity. Conversely, fed mice experienced augmented post-exercise food intake, with no effects on POMC neuron activity. Regardless of pre-exercise energy status, tyrosine hydroxylase and SIM1 neuron activity in the paraventricular nucleus was elevated, as well as NPY/AgRP neuron activity in the arcuate nucleus. Notably, these neuronal changes were independent from changes in pSTAT3tyr705 and pERKthr202/tyr204 signaling. Overall, these results suggest fasted high intensity exercise may be beneficial for suppressing food intake, possibly due to hypothalamic POMC neuron excitation. Furthermore, this study identifies a novel role for pre-exercise energy status to differentially modify post-exercise feeding behavior and hypothalamic neuron activity, which may explain the inconsistent results from studies investigating exercise as a weight loss intervention.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Energy Status Differentially Modifies Feeding Behavior and POMCARC Neuron Activity After Acute Treadmill Exercise in Untrained Mice

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Several key elements of the neural signature of individuals with anorexia nervosa have been recapitulated in the activity-based anorexia model, such as disrupted reward signaling (18)(19)(20) and reduced serotonin signing (21)(22)(23), supporting construct validity. The ability to perform neurogenetic manipulations of discrete circuits and pathways in these models is accelerating progress in the understanding of mechanisms driving pathological eating behaviors (20,24,25). However, because they are designed to induce a specific type of outcome (i.e., anorexia vs. binge eating), they cannot be used to identify determinants of stress-induced increases vs.…”

Section: Introductionmentioning

confidence: 99%

A Framework for Developing Translationally Relevant Animal Models of Stress-Induced Changes in Eating Behavior

François¹,

Fernández-Gayol²,

Zeltser³

2022

Biological Psychiatry

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

In pursuit of biomarkers for predicting susceptibility to activity‐based anorexia in adolescent female rats

Milton

Patton

O’Keeffe

et al. 2022

Intl J Eating Disorders

View full text Add to dashboard Cite

Objective Identifying risk factors that contribute to the development of anorexia nervosa (AN) is critical for the implementation of early intervention strategies. Anxiety, obsessive–compulsive behavior, and immune dysfunction may be involved in the development of AN; however, their direct influence on susceptibility to the condition remains unclear. Here, we used the activity‐based anorexia (ABA) model to examine whether activity, anxiety‐like behavior, compulsive behavior, and circulating immune markers predict the subsequent development of pathological weight loss. Method Female Sprague–Dawley rats (n = 44) underwent behavioral testing before exposure to ABA conditions after which they were separated into susceptible and resistant subpopulations. Blood was sampled before behavioral testing and after recovery from ABA to screen for proinflammatory cytokines. Results Rats that were vulnerable to pathological weight loss differed significantly from resistant rats on all key ABA parameters. While the primary measures of anxiety‐like or compulsive behavior were not shown to predict vulnerability to ABA, increased locomotion and anxiety‐like behavior were both associated with the extent of weight loss in susceptible but not resistant animals. Moreover, the change in expression of proinflammatory markers IL‐4 and IL‐6 evoked by ABA was associated with discrete vulnerability factors. Intriguingly, behavior related to risk assessment was shown to predict vulnerability to ABA. Discussion We did not find undisputable behavioral or immune predictors of susceptibility to pathological weight loss in the ABA rat model. Future research should examine the role of cognition in the development of ABA, dysfunction of which may represent an endophenotype linking anorectic, anxiety‐like and compulsive behavior. Public Significance Anorexia nervosa (AN) has among the highest mortality rates of all psychiatric disorders and treatment options remain limited in their efficacy. Understanding what types of risk factors contribute to the development of AN is essential for implementing early intervention strategies. This study describes how some of the most common psychological features of AN could be used to predict susceptibility to pathological weight loss in a well‐established animal model.

show abstract

AgRP neurons control compulsive exercise and survival in an activity-based anorexia model

Cited by 51 publications

References 38 publications

Energy Status Differentially Modifies Feeding Behavior and POMCARC Neuron Activity After Acute Treadmill Exercise in Untrained Mice

Energy Status Differentially Modifies Feeding Behavior and POMCARC Neuron Activity After Acute Treadmill Exercise in Untrained Mice

A Framework for Developing Translationally Relevant Animal Models of Stress-Induced Changes in Eating Behavior

In pursuit of biomarkers for predicting susceptibility to activity‐based anorexia in adolescent female rats

Contact Info

Product

Resources

About