Leptin and the brain: Influences on brain development, cognitive functioning and psychiatric disorders

Farr, Olivia M.; Tsoukas, Michael A.; Mantzoros, Christos S.

doi:10.1016/j.metabol.2014.07.004

Cited by 114 publications

(103 citation statements)

References 250 publications

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“…In vivo studies have shown that leptin treatment can reduce Aβ42 by facilitating its clearance via reducing β-secretase activity and increasing APOE-dependent Aβ uptake and hyperphosphorylated tau levels in a dose-dependent and synergistic manner with insulin [39,40] and improve behavioral abnormalities and cognition in PwAD [41,42]. We observed reduced serum leptin levels in our study which are in agreement with other studies [43,44,45,46].…”

Section: Discussionsupporting

confidence: 92%

Multifactorial Analysis of a Biomarker Pool for Alzheimer Disease Risk in a North Indian Population

Talwar

Grover

Sinha

et al. 2017

Dement Geriatr Cogn Disord

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Background: Alzheimer disease (AD) is a progressive neurodegenerative disease with a complex multifactorial etiology. Here, we aim to identify a biomarker pool comprised of genetic variants and blood biomarkers as predictor of AD risk. Methods: We performed a case-control study involving 108 cases and 159 non-demented healthy controls to examine the association of multiple biomarkers with AD risk. Results: The APOE genotyping revealed that ε4 allele frequency was significantly high (p value = 0.0001, OR = 2.66, 95% CI 1.58-4.46) in AD as compared to controls, whereas ε2 (p = 0.0430, OR = 0.29, CI 0.07-1.10) was overrepresented in controls. In biochemical assays, significant differences in levels of total copper, free copper, zinc, copper/zinc ratio, iron, epidermal growth factor receptor (EGFR), leptin, and albumin were also observed. The AD risk score (ADRS) as a linear combination of 6 candidate markers involving age, education status, APOE ε4 allele, levels of iron, Cu/Zn ratio, and EGFR was created using stepwise linear discriminant analysis. The area under the ROC curve of the ADRS panel for predicting AD risk was significantly high (AUC = 0.84, p < 0.0001, 95% CI 0.78-0.89, sensitivity = 70.0%, specificity = 83.8%) compared to individual parameters. Conclusion: These findings support the multifactorial etiology of AD and demonstrate the ability of a panel involving 6 biomarkers to discriminate AD cases from non-demented healthy controls.

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Section: Discussionsupporting

confidence: 92%

Multifactorial Analysis of a Biomarker Pool for Alzheimer Disease Risk in a North Indian Population

Talwar

Grover

Sinha

et al. 2017

Dement Geriatr Cogn Disord

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“…It binds to the leptin receptor (LEPR), which is expressed in the hypothalamus, where it influences satiety and plays an important role in the regulation of the hypothalamus-pituitary-gonadal axis. LEPR is also expressed in other brain regions such as the cortex, midbrain and hindbrain, where its role is not completely clear yet [1]. …”

Section: Introductionmentioning

confidence: 99%

Novel Leptin Receptor Mutations Identified in Two Girls with Severe Obesity Are Associated with Increased Bone Mineral Density

Hannema¹,

Wit²,

Houdijk³

et al. 2016

Horm Res Paediatr

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Background: Recessive mutations in the leptin receptor (LEPR) are a rare cause of hyperphagia and severe early-onset obesity. To date, the phenotype has only been described in 25 obese children, some of whom also had altered immune function, hypogonadotropic hypogonadism, reduced growth hormone secretion, hypothalamic hypothyroidism or reduced adult height. We provide a detailed description of the phenotype of 2 affected girls to add to this knowledge. Methods: Whole-exome sequencing and targeted sequencing were used to detect the LEPR mutations. RNA analysis was performed to assess the effect of splice-site mutations. Results: In 2 unrelated girls with severe obesity, three novel LEPR mutations were detected. Longitudinal growth data show normal childhood growth, and in the older girl, a normal adult height despite hypogonadotropic hypogonadism and the lack of an obvious pubertal growth spurt. Bone age is remarkably advanced in the younger (prepubertal) girl, and bone mineral density (BMD) is high in both girls, which might be directly or indirectly related to leptin resistance. Conclusion: The spectrum of clinical features of LEPR deficiency may be expanded with increased BMD. Future observations in LEPR-deficient subjects should help further unravel the role of leptin in human bone biology.

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“…There is growing consensus that leptin has a role in hippocampal synaptogenesis and memory formation (Farr et al 2015;Harvey et al 2005). Leptin receptors are abundantly expressed in the hippocampus (Shanley et al 2002) and bilateral injection of leptin into the hippocampus improves memory processing and retention in mice (Farr et al 2006) while rats and mice deficient in leptin receptors exhibit profound deficits in spatial learning and memory (Li et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Serum Leptin and Cortisol, Related to Acutely Perceived Academic Examination Stress and Performance in Female University Students

Haleem

Inam

Haider

et al. 2015

Appl Psychophysiol Biofeedback

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Leptin, identified as an antiobesity hormone, also has important role in responses to stress and processing of memory. This study was designed to determine effects of academic examination stress-induced changes in serum leptin and its impact on academic performance. Eighty five healthy female students (age 19-21 years; BMI 21.9 ± 1.6) were recruited for the study. Serum leptin and cortisol were monitored at base line (beginning of academic session) and on the day of examination; using a standardized ELISA kit. Acute perception of academic examination stress was determined with the help of a questionnaire derived from Hamilton Anxiety Scale and self report of stress perception. Academic performance was evaluated by the percentage of marks obtained in the examination. Serum cortisol levels were positively correlated (p < 0.01) with the subjective perception of examination stress but not with academic performance. There was an inverted U-shape relationship between level of stress and academic performance. Leptin increased in all stress groups and correlated (p < 0.01) positively with academic performance. There was an inverted U-shape relationship between level of stress and circulating leptin. The findings suggest the peptide hormone, leptin, is a biomarker of stress perception and a mediator of facilitating effects of stress on cognition.

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Leptin and the brain: Influences on brain development, cognitive functioning and psychiatric disorders

Cited by 114 publications

References 250 publications

Multifactorial Analysis of a Biomarker Pool for Alzheimer Disease Risk in a North Indian Population

Multifactorial Analysis of a Biomarker Pool for Alzheimer Disease Risk in a North Indian Population

Novel Leptin Receptor Mutations Identified in Two Girls with Severe Obesity Are Associated with Increased Bone Mineral Density

Serum Leptin and Cortisol, Related to Acutely Perceived Academic Examination Stress and Performance in Female University Students

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