The Role of Leptin in the Development of the Cerebral Cortex in Mouse Embryos

Udagawa, Jun; Hashimoto, Ryuju; Suzuki, Hiroaki; Hatta, Toshihisa; Sotomaru, Yusuke; Hioki, Kyoji; Kagohashi, Yukiko; Nomura, Tatsuji; Minami, Yasuhiro; Otani, Hiroki

doi:10.1210/en.2005-0791

Cited by 104 publications

(72 citation statements)

References 66 publications

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“…Indeed, leptin has been found to act as an anti-apoptotic hormone under stress conditions (Russo et al, 2004). A role for leptin in neurogenesis and neurodevelopment is strengthened by the observations of Udagaw and others (Udagawa et al, 2006) that leptin stimulates the proliferation of precursor cells committed to neuronal differentiation, and promotes neuronal terminal differentiation. Recent work by Guo et al (2007) suggests that leptin serves a neurotrophic function in the developing and adult hippocampus by enhancing mitochondrial resistance to apoptosis and excitoxicity.…”

Section: Discussionmentioning

confidence: 95%

Serum leptin level and cognition in the elderly: Findings from the Health ABC Study

Holden

Lindquist

Tylavsky

et al. 2009

Neurobiology of Aging

196

142

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Leptin is a peptide hormone secreted by adipocytes. It has been shown to modulate production and clearance of amyloid beta (Aβ) in rodent models. We sought to determine if serum leptin was associated with cognitive decline in the elderly.We studied 2871 well-functioning elders, aged 70-79, who were enrolled in a prospective study. Serum leptin concentrations were measured at baseline and analyzed by mean ± 1 SD. Clinically significantly cognitive decline over 4 years was defined as ≥ 5 point drop on the Modified Mini Mental State Exam (3MS).Compared to those in the lower leptin groups, elders in the high leptin group had less cognitive decline, 20.5% vs. 24.7% (OR=0.79 95% CI 0.61-1.02, p=0.07). After adjustment for demographic and clinical variables, including body mass index and total percent body fat, those in the high leptin group had significantly less likelihood of cognitive decline, OR=0.66 (95% CI 0.48-0.91). We conclude that in elderly individuals, higher serum leptin appears to protect against cognitive decline, independent of comorbidites and body fat. HHS Public Access

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Section: Discussionmentioning

confidence: 95%

Serum leptin level and cognition in the elderly: Findings from the Health ABC Study

Holden

Lindquist

Tylavsky

et al. 2009

Neurobiology of Aging

196

142

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“…The association between fasting plasma leptin concentrations and reduced GM volumes of some cortical (i.e., inferior frontal operculum and postcentral gyrus) and striatal (i.e., putamen) areas may be unexpected, given the reported neurotrophic action of leptin on the brains of ob/ ob mice [23][24][25]. These mice, however, have complete leptin deficiency [23][24][25].…”

Section: Discussionmentioning

confidence: 99%

“…These mice, however, have complete leptin deficiency [23][24][25]. It is not known if the neurotrophic effects of leptin on mice with leptin deficiency are relevant to the neuronal effects of leptin in lean or obese persons, who have normal or high leptin concentrations, respectively [9].…”

Section: Discussionmentioning

confidence: 99%

Relationships between plasma leptin concentrations and human brain structure: A voxel-based morphometric study

Pannacciulli¹,

Le²,

Chen

et al. 2007

Neuroscience Letters

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We have previously demonstrated that obese people have reduced grey matter (GM) in several brain areas, including regions implicated in the regulation of taste (i.e., inferior frontal operculum and postcentral gyrus), reward (i.e., putamen), and behavioral processing (i.e., middle frontal gyrus), compared with their lean counterparts. It is well established that the brain may serve as a direct target for adiposity signals, one of the most important being leptin. We investigated the relationships between fasting plasma leptin concentrations and brain tissue composition in a group of 32 young adult Caucasians (12M/20F, age 32±1 y, body fat 29±1%, mean ± SE) with normal glucose tolerance by using voxel-based morphometry of magnetic resonance imaging scans. Fasting plasma leptin concentrations were positively correlated with grey matter (GM) volumes of the left cerebellum and left inferior temporal gyrus and negatively associated with GM volumes of the left inferior frontal operculum, left postcentral gyrus, and right putamen (P<0.001, uncorrected for multiple comparisons) after adjustment for sex, percent body fat, age, fasting plasma insulin concentrations (i.e., the major determinants of plasma leptin), and global GM volume (thus allowing for an assessment of regional effects only). This study showed an independent, negative correlation between fasting plasma leptin concentrations, which are increased in obesity, and the volumes of GM in brain areas where obese people have reduced GM compared to their lean counterparts. These relationships may explain some of the abnormalities in brain morphology recently found to be associated with excess body fatness.

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“…It has been reported that leptin maintains neuronal stem cells and progenitor cells and is related to neuronal and glial development in the mouse embryonic brain (Udagawa et al 2006a;Udagawa et al 2006b), suggesting that leptin plays an important role in embryonic cerebrocortical development. It is also reported that factors expressed during the developmental stage of the CNS exhibits an overexpression pattern by neoplastic cells in mature brain (Merrill and Oldfield 2005;Plata-Salaman 1991;Trojan et al 2007).…”

Section: Leptin Increases the Migration And Invasion Of C6 Glioma Cellsmentioning

confidence: 99%

Leptin induces migration and invasion of glioma cells through MMP‐13 production

Yeh

Lee

et al. 2008

Glia

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Leptin, the product of the obses gene, plays an important role in the regulation of body weight by coordinating metabolism, feeding behavior, energy balance and neuroendocrine responses. However, central regulation of leptin gene expression is different from that in the adipocytes. In addition, leptin has been found in many tumor cell lines and has been shown to have mitogenic and angiogenic activity in a number of cell types. Glioma is the most common primary adult brain tumor with poor prognosis due to the spreading of tumor cell to the other regions of brain easily. Here we found that malignant C6 glioma cells expressed more leptin and leptin receptors than non-malignant astrocytes. Furthermore, it was found that exogenous application of leptin enhanced the migration and invasion of C6 glioma cells. In addition, we found that the expression of matrix metalloproteinase-13 (MMP-13) but not of MMP-2 and MMP-9 was increased in response to leptin stimulation. The leptin-induced increase of cell migration and invasion was antagonized by MMP-13 neutralizing antibody or silencing MMP-13. The up-regulation of MMP-13 induced by leptin was mainly through p38 MAP kinase and NF-κB pathway. In addition, migration-prone sublines demonstrate that cells with increasing migration ability had more expression of MMP-13 and leptin. Taken together, these results indicate that leptin enhanced migration and invasion of C6 glioma cells through the increase of 2

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The Role of Leptin in the Development of the Cerebral Cortex in Mouse Embryos

Cited by 104 publications

References 66 publications

Serum leptin level and cognition in the elderly: Findings from the Health ABC Study

Serum leptin level and cognition in the elderly: Findings from the Health ABC Study

Relationships between plasma leptin concentrations and human brain structure: A voxel-based morphometric study

Leptin induces migration and invasion of glioma cells through MMP‐13 production

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