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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accumulating evidence indicates that diet and body weight are important factors associated with Alzheimer's disease (AD), with a significant increase in AD risk linked to mid-life obesity, and weight loss frequently occurring in the early stages of AD. This has fuelled interest in the hormone leptin, as it is an important hypothalamic regulator of food intake and body weight, but leptin also markedly influences the functioning of the hippocampus; a key brain region that degenerates in AD. Increasing evidence indicates that leptin has cognitive enhancing properties as it facilitates the cellular events that underlie hippocampal-dependent learning and memory. However, significant reductions in leptin's capacity to regulate hippocampal synaptic function occurs with age and dysfunctions in the leptin system are associated with an increased risk of AD. Moreover, leptin is a potential novel target in AD as leptin treatment has beneficial effects in various models of AD. Here we summarise recent advances in leptin neurobiology with particular focus on regulation of hippocampal synaptic function by leptin and the implications of this for neurodegenerative disorders like AD. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'
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PMID:Food for thought: Leptin regulation of hippocampal function and its role in Alzheimer's disease. 2898 37

For decades the brain was erroneously considered an insulin insensitive organ. Although gaps in our knowledge base remain, conceptual frameworks are starting to emerge to provide insight into the mechanisms through which insulin facilitates critical brain functions like metabolism, cognition, and motivated behaviors. These diverse physiological and behavioral activities highlight the region-specific activities of insulin in the CNS; that is, there is an anatomical context to the activities of insulin in the CNS. Similarly, there is also a temporal context to the activities of insulin in the CNS. Indeed, brain insulin receptor activity can be conceptualized as a continuum in which insulin promotes neuroplasticity from development into adulthood where it is an integral part of healthy brain function. Unfortunately, brain insulin resistance likely contributes to neuroplasticity deficits in obesity and type 2 diabetes mellitus (T2DM). This neuroplasticity continuum can be conceptualized by the mechanisms through which insulin promotes cognitive function through its actions in brain regions like the hippocampus, as well as the ability of insulin to modulate motivated behaviors through actions in brain regions like the nucleus accumbens and the ventral tegmental area. Thus, the goals of this review are to highlight these anatomical, temporal, and functional contexts of insulin activity in these brain regions, and to identify potentially critical time points along this continuum where the transition from enhancement of neuroplasticity to impairment may take place. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'
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PMID:Insulin-mediated synaptic plasticity in the CNS: Anatomical, functional and temporal contexts. 2921 83

Major depressive disorder and bipolar disorder are highly prevalent and disabling conditions. Cognition is considered a core domain of their psychopathology and a principle mediator of psychosocial impairment, disproportionately accounting for overall illness-associated costs. There are few interventions with replicated evidence of efficacy in treating cognitive deficits in mood disorders. Evidence also indicates that cognitive deficits are associated with obesity and involve significant impairment across multiple domains. Conversely, weight-loss interventions, such as physical exercise and bariatric surgery, have been shown to beneficially affect cognitive function. This convergent phenomenology suggests that currently available agents that target metabolic systems may also be capable of mitigating deficits in cognitive functions, and are, therefore, candidates for repurposing. The incretin glucagon-like peptide-1 (GLP-1) is a hormone secreted by intestinal epithelial cells. GLP-1 receptors (GLP-1R) are widely expressed in the central nervous system. Activation of GLP-1R leads to facilitation of glucose utilization and antiapoptotic effects in various organs. Pre-clinical trials have demonstrated significant neuroprotective effects of GLP-1, including protection from cell death, promotion of neuronal differentiation and proliferation; and facilitation of long-term potentiation. Liraglutide is a GLP-1R agonist that has been approved for the treatment of type 2 diabetes mellitus and obesity. Convergent preclinical and clinical evidence, including a proof-of-concept pilot study from group, has suggested that liraglutide may improve objective measures of cognitive function in adults with mood disorders. The safety and availability of GLP-1R agonists indicate that they are promising candidates for repurposing, and that they may be viable therapeutic options for mood disorders. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'
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PMID:Cognitive dysfunction and metabolic comorbidities in mood disorders: A repurposing opportunity for glucagon-like peptide 1 receptor agonists? 2948 15

Recent clinical and epidemiological observations point to a correlation between disorders of energy metabolism, such as obesity and diabetes, and cognitive decline and dementia. Many studies indicate that these age-related conditions closely interact with each other, but the underlying molecular and physiological mechanisms for such correlations are largely unknown. Insulin and leptin, hormones classically implicated in diabetes and obesity, are gaining increasing attention for their participation in cognitive processes and memory. Disrupted signaling by those hormones is associated with impaired brain function. The current review discusses how restoration of insulin and leptin signaling in the brain may attenuate neuronal damage and promote cognition. We further discuss potential therapeutic approaches involving the use of insulin and leptin as cognitive enhancers in the context of metabolic disorders and Alzheimer's disease. This article is part of the special issue entitled 'The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders'.
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PMID:Insulin and leptin as potential cognitive enhancers in metabolic disorders and Alzheimer's disease. 3234 8