Interplay of circulating leptin and obesity in cognition and cerebral volumes in older adults

Zonneveld, Michelle; Noordam, Raymond; Heemst, Diana van; Mooijaart, Simon P.; Sabayan, Behnam; Jukema, J. Wouter; Trompet, Stella

doi:10.1016/j.peptides.2020.170424

Cited by 10 publications

(9 citation statements)

References 47 publications

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“…In contrast, research on associations between leptin and brain structures/functions in humans is still sparse (Paz-Filho, 2016). However, significant leptin effects on neuronal tissue composition, functional magnetic resonance imaging (MRI) amygdala activation and (whole) amygdala volume have been described in preliminary studies in leptin-deficient patients (Frank et al, 2011(Frank et al, , 2013Matochik et al, 2005) and older adults (Zonneveld et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Differential alterations of amygdala nuclei volumes in acutely ill patients with anorexia nervosa and their associations with leptin levels

et al. 2022

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Background The amygdala is a subcortical limbic structure consisting of histologically and functionally distinct subregions. New automated structural magnetic resonance imaging (MRI) segmentation tools facilitate the in vivo study of individual amygdala nuclei in clinical populations such as patients with anorexia nervosa (AN) who show symptoms indicative of limbic dysregulation. This study is the first to investigate amygdala nuclei volumes in AN, their relationships with leptin, a key indicator of AN-related neuroendocrine alterations, and further clinical measures. Methods T1-weighted MRI scans were subsegmented and multi-stage quality controlled using FreeSurfer. Left/right hemispheric amygdala nuclei volumes were cross-sectionally compared between females with AN (n = 168, 12–29 years) and age-matched healthy females (n = 168) applying general linear models. Associations with plasma leptin, body mass index (BMI), illness duration, and psychiatric symptoms were analyzed via robust linear regression. Results Globally, most amygdala nuclei volumes in both hemispheres were reduced in AN v. healthy control participants. Importantly, four specific nuclei (accessory basal, cortical, medial nuclei, corticoamygdaloid transition in the rostral-medial amygdala) showed greater volumetric reduction even relative to reductions of whole amygdala and total subcortical gray matter volumes, whereas basal, lateral, and paralaminar nuclei were less reduced. All rostral-medially clustered nuclei were positively associated with leptin in AN independent of BMI. Amygdala nuclei volumes were not associated with illness duration or psychiatric symptom severity in AN. Conclusions In AN, amygdala nuclei are altered to different degrees. Severe volume loss in rostral-medially clustered nuclei, collectively involved in olfactory/food-related reward processing, may represent a structural correlate of AN-related symptoms. Hypoleptinemia might be linked to rostral-medial amygdala alterations.

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Section: Introductionmentioning

confidence: 99%

Differential alterations of amygdala nuclei volumes in acutely ill patients with anorexia nervosa and their associations with leptin levels

et al. 2022

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“…Possible mechanisms contributing to lower synaptic density as a function of BMI include elevated systemic inflammation and neuroimmune activation [25,51]. In addition, obesity or consumption of a high-fat diet is associated with increase in leptin levels and alterations in glucocorticoid signaling, of which both can impact neurotrophic factors such as BDNF/TrkB and mTor signaling in ways that could contribute to dendritic atrophy and synaptic loss [25,[52][53][54][55][56]. Consistent with this potential mechanism, in leptin-receptordeficient mouse model of obesity, plasma corticosterone was elevated and associated with reduced BDNF protein expression and hippocampal synaptic deficits, along with impaired spatial memory, with these phenotypes being "rescued" by treatment with the glucocorticoid synthesis inhibitor metyrapone [57].…”

Section: Discussionmentioning

confidence: 99%

Lower synaptic density is associated with psychiatric and cognitive alterations in obesity

Asch

Holmes

Jastreboff

et al. 2021

Neuropsychopharmacol.

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Obesity is a serious medical condition that often co-occurs with stress-related psychiatric disorders. It is recognized that the brain plays a key role in the (patho)physiology of obesity and that there is a bidirectional relationship between obesity and psychopathology, yet molecular mechanisms altered in obesity have not been fully elucidated. Thus, we investigated relationships between obesity and synaptic density in vivo using the radioligand [ 11 C]UCB-J (which binds to synaptic glycoprotein SV2A) and positron emission tomography in individuals with obesity, and with or without stress-related psychiatric disorders. Regions of interest were the dorsolateral prefrontal cortex, orbitofrontal cortex, ventromedial, amygdala, hippocampus, and cerebellum. Forty individuals with a body mass index (BMI) ≥ 25 kg/m 2 (overweight/obese), with (n = 28) or without (n = 12) psychiatric diagnosis, were compared to 30 age-and sex-matched normal weight individuals (BMI < 25), with (n = 14) or without (n = 16) psychiatric diagnosis. Overall, significantly lower synaptic density was observed in overweight/obese relative to normal weight participants (η p 2 = 0.193, F = 2.35, p = 0.042). Importantly, in participants with stress-related psychiatric diagnoses, we found BMI to be negatively correlated with synaptic density in all regions of interest (p ≤ 0.03), but no such relationship observed for mentally healthy controls (p ≥ 0.68). In the stress-related psychiatric groups, dorsolateral prefrontal cortex synaptic density was negatively associated with measures of worry (r = −0.46, p = 0.01), tension/anxiety (r = −0.38, p = 0.04), fatigue (r = −0.44, p = 0.02), and attentional difficulties (r = −0.44, p = 0.02). In summary, the findings of this novel in vivo experiment suggest compounding effects of obesity and stress-related psychopathology on the brain and the associated symptomatology that may impact functioning. This offers a novel biological mechanism for the relationship between overweight/obesity and stress-related psychiatric disorders that may guide future intervention development efforts.

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“…О жирение в среднем возрасте ассоциировано со снижением когнитивных функций, что подтверждено в разных эпидемиологических исследованиях -Health Aging and Body Composition Study (Health ABC study), the Baltimore Longitudinal Study on Aging (BLSA), the Neurological Diseases in Central Spain (NEDICES), the Women's Health Initiative (WHI) [1]. Высокий индекс массы тела (ИМТ) -модифицируемый фактор риска в случае некоторых неблагоприятных последствий для здоровья, таких как сердечно-сосудистые заболевания, сахарный диабет 2-го типа и деменция [2]. Жировая ткань регулирует функции гиппокампа, ответственного за когнитивные способности, посредством высвобождения адипокинов, которые могут прямо или косвенно модулировать нейронную пластичность и нейровоспаление [3].…”

Section: оригинальные исследованияunclassified

Anthropometric, metabolic parameters and cognitive functions investigation in patients with obesity treated with liraglutide 3 mg

Самойлова¹,

Матвеева²,

Oleynik³

2022

Endocrinology: News, Opinions, Training

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Interplay of circulating leptin and obesity in cognition and cerebral volumes in older adults

Cited by 10 publications

References 47 publications

Differential alterations of amygdala nuclei volumes in acutely ill patients with anorexia nervosa and their associations with leptin levels

Differential alterations of amygdala nuclei volumes in acutely ill patients with anorexia nervosa and their associations with leptin levels

Lower synaptic density is associated with psychiatric and cognitive alterations in obesity

Anthropometric, metabolic parameters and cognitive functions investigation in patients with obesity treated with liraglutide 3 mg

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