Decreased excitability of leptin-sensitive anterior insula pyramidal neurons in a rat model of compulsive food demand

Kirson, Dean; Bagsic, Samantha R. Spierling; Murphy, J T; Chang, Hang; Vlkolinský, Roman; Pucci, Sarah N.; Prinzi, Julia; Williams, Casey A.; Fang, Savannah Y.; Roberto, Marisa; Zorrilla, Eric P.

doi:10.1016/j.neuropharm.2022.108980

Cited by 10 publications

(4 citation statements)

References 134 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Female rats with intermittent access to sucrose–chocolate‐flavoured pellets show a positive correlation between circulating leptin levels, increased motivation to eat, and compulsive sucrose intake (Spierling et al ., 2020), suggesting that decreased leptin signalling in the brain, resulting from leptin resistance, causes dysregulated eating. At the mechanistic level, rats exposed to intermittent access to sucrose show lower inhibitory effects of leptin on anterior insula neurons compared with those fed a regular chow diet (Kirson et al ., 2022), suggesting direct actions of leptin in food reward circuits. Still, these findings remain incompletely understood as others have shown that intermittent access to sucrose does not alter LEPR levels in the hypothalamus (Soto et al ., 2015), suggesting a site‐specific effect of leptin in brain regions associated with addiction‐like behaviour.…”

Section: Exploring the Roles Of Leptin Glucocorticoids And Glp1 In Ea...mentioning

confidence: 99%

The interplay between leptin, glucocorticoids, and GLP1 regulates food intake and feeding behaviour

Perez‐Leighton,

Kerr,

Scherer

et al. 2023

Biological Reviews

View full text Add to dashboard Cite

Nutritional, endocrine, and neurological signals converge in multiple brain centres to control feeding behaviour and food intake as part of the allostatic regulation of energy balance. Among the several neuroendocrine systems involved, the leptin, glucocorticoid, and glucagon‐like peptide 1 (GLP1) systems have been extensively researched. Leptin is at the top hierarchical level since its complete absence is sufficient to trigger severe hyperphagia. Glucocorticoids are key regulators of the energy balance adaptation to stress and their sustained excess leads to excessive adiposity and metabolic perturbations. GLP1 participates in metabolic adaptation to food intake, regulating insulin secretion and satiety by parallel central and peripheral signalling systems. Herein, we review the brain and peripheral targets of these three hormone systems that integrate to regulate food intake, feeding behaviour, and metabolic homeostasis. We examine the functional relationships between leptin, glucocorticoids, and GLP1 at the central and peripheral levels, including the cross‐regulation of their circulating levels and their cooperative or antagonistic actions at different brain centres. The pathophysiological roles of these neuroendocrine systems in dysregulated intake are explored in the two extremes of body adiposity – obesity and lipodystrophy – and eating behaviour disorders.

show abstract

Section: Exploring the Roles Of Leptin Glucocorticoids And Glp1 In Ea...mentioning

confidence: 99%

The interplay between leptin, glucocorticoids, and GLP1 regulates food intake and feeding behaviour

Perez‐Leighton,

Kerr,

Scherer

et al. 2023

Biological Reviews

View full text Add to dashboard Cite

show abstract

“…Cross-sectional human imaging studies do not, however, address whether heightened insular activation is pre-existing in nature or a consequence of overconsuming palatable food. Rodent studies have provided some insight in this regard; for example, intermittent access to a palatable diet induces functional adaptations in insular pyramidal neurons [ 22 ] and targeted optogenetic inhibition of glutamatergic efferents of the anterior insula to nucleus accumbens (NAc) reduces compulsive food self-administration in female rats [ 23 ]. Recent evidence indicates that the insula receives dense glutamatergic innervation from various brain loci involved in reward and appetitive motivation [ 24 ], suggesting that glutamatergic projections to the insula constitute prime candidates that drive stress-induced binge eating.…”

Section: Introductionmentioning

confidence: 99%

A paraventricular thalamus to insular cortex glutamatergic projection gates “emotional” stress-induced binge eating in females

Anversa

Campbell

Ch’ng

et al. 2023

Neuropsychopharmacol.

View full text Add to dashboard Cite

It is well-established that stress and negative affect trigger eating disorder symptoms and that the brains of men and women respond to stress in different ways. Indeed, women suffer disproportionately from emotional or stress-related eating, as well as associated eating disorders such as binge eating disorder. Nevertheless, our understanding of the precise neural circuits driving this maladaptive eating behavior, particularly in women, remains limited. We recently established a clinically relevant model of ‘emotional’ stress-induced binge eating whereby only female mice display binge eating in response to an acute “emotional” stressor. Here, we combined neuroanatomic, transgenic, immunohistochemical and pathway-specific chemogenetic approaches to investigate whole brain functional architecture associated with stress-induced binge eating in females, focusing on the role of Vglut2 projections from the paraventricular thalamus (PVTVglut2+) to the medial insular cortex in this behavior. Whole brain activation mapping and hierarchical clustering of Euclidean distances revealed distinct patterns of coactivation unique to stress-induced binge eating. At a pathway-specific level, PVTVglut2+ cells projecting to the medial insular cortex were specifically activated in response to stress-induced binge eating. Subsequent chemogenetic inhibition of this pathway suppressed stress-induced binge eating. We have identified a distinct PVTVglut2+ to insular cortex projection as a key driver of “emotional” stress-induced binge eating in female mice, highlighting a novel circuit underpinning this sex-specific behavior.

show abstract

“…Early reports using these procedures examined the essential value of solid foods across a variety of species including humans ( Epstein et al, 2018 ), monkeys ( Hursh, 1978 ; Hursh & Silberberg, 2008 ), fowl ( Dawkins, 1983 ; Tsunematsu, 2001 ), and rodents ( Bauman et al, 1996 ; Galuska et al, 2011 ; Hursh & Natelson, 1981 ; Hursh & Silberberg, 2008 ). More recently, studies examining effects of diet-induced obesity in rodents have found upward shifts in the demand curve that result in increases in Q 0 , Pmax and Rmax ( Batten et al, 2020 ; Kirson et al, 2022 ; Rasmussen et al, 2010 ; Townsend et al, 2015 ). These results are more consistent with observations in humans ( Boswell & Kober, 2016 ; Jastreboff et al, 2013 ), and oppose effects of reduced motivation found with fixed ratio or progressive ratio procedures in rodents (e.g., ( Vendruscolo et al, 2010 ; Vollbrecht et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Applying behavioral economics-based approaches to examine the effects of liquid sucrose consumption on motivation

Finnell

Ferrario

2023

Appetite

View full text Add to dashboard Cite

Decreased excitability of leptin-sensitive anterior insula pyramidal neurons in a rat model of compulsive food demand

Cited by 10 publications

References 134 publications

The interplay between leptin, glucocorticoids, and GLP1 regulates food intake and feeding behaviour

The interplay between leptin, glucocorticoids, and GLP1 regulates food intake and feeding behaviour

A paraventricular thalamus to insular cortex glutamatergic projection gates “emotional” stress-induced binge eating in females

Applying behavioral economics-based approaches to examine the effects of liquid sucrose consumption on motivation

Contact Info

Product

Resources

About