Hippocampal insulin resistance and altered food decision-making as players on obesity risk

Mucellini, Amanda Brondani; Fonseca, Natasha Kim de Oliveira da; Manfro, Gisele Gus; Silveira, Patrícia Pelufo

doi:10.1016/j.neubiorev.2017.03.011

Cited by 14 publications

(10 citation statements)

References 227 publications

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“…Inflammation caused by obesity may be an important factor associated with insulin resistance [41]. Previous studies have also documented that adolescent mice fed with high-fat diets present an increased level of inflammation in hippocampal tissues, and insulin signaling is also significantly blocked [42,43]. As a bridge between inflammation and insulin, inflammatory factors promote the phosphorylation of IRS-1 at the Ser307 site by activating JNK phosphorylation, thereby hindering insulin signaling and exacerbating insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Swimming Suppresses Cognitive Decline of HFD-Induced Obese Mice through Reversing Hippocampal Inflammation, Insulin Resistance, and BDNF Level

Zhang

Liang

et al. 2022

Nutrients

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Obesity is an important public health problem nowadays. Long-term obesity can trigger a series of chronic diseases and impair the learning and memory function of the brain. Current studies show that scientific exercise can effectively improve learning and memory capacity, which also can provide benefits for obese people. However, the underlying mechanisms for the improvement of cognitive capacity under the status of obesity still need to be further explored. In the present study, the obesity-induced cognition-declined model was established using 4-week-old mice continuously fed with a high-fat diet (HFD) for 12 weeks, and then the model mice were subjected to an 8-week swimming intervention and corresponding evaluation of relevant indicators, including cognitive capacity, inflammation, insulin signal pathway, brain-derived neurotrophic factor (BNDF), and apoptosis, for exploring potential regulatory mechanisms. Compared with the mice fed with regular diets, the obese mice revealed the impairment of cognitive capacity; in contrast, swimming intervention ameliorated the decline in cognitive capacity of obese mice by reducing inflammatory factors, inhibiting the JNK/IRS-1/PI3K/Akt signal pathway, and activating the PGC-1α/BDNF signal pathway, thereby suppressing the apoptosis of neurons. Therefore, swimming may be an important interventional strategy to compensate for obesity-induced cognitive impairment.

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Section: Discussionmentioning

confidence: 99%

Swimming Suppresses Cognitive Decline of HFD-Induced Obese Mice through Reversing Hippocampal Inflammation, Insulin Resistance, and BDNF Level

Zhang

Liang

et al. 2022

Nutrients

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“…IR central anatomical distribution overlaps with neurotransmitter systems [e.g., dopamine (DA), serotonin, g-aminobutyric (GABA), glutamate] that are major players in the mechanism of neuronal communication. A wealth of studies demonstrate the importance of insulin signaling in many central nervous system functions, such as synaptogenesis, synaptic plasticity, neuroprotection, memory, and cognition, including long-term potentiation and depression (LTP and LTD) [12], attention, sensitivity to reward, inhibitory control [13], energy balance, and eating behavior [14]. Insulin and its receptor play a key role in the dynamics of dendrite formation, spine density, neurite growth, and neuronal development [15].…”

Section: Central Action Of Insulinmentioning

confidence: 99%

Early adversity and insulin: neuroendocrine programming beyond glucocorticoids

Batra

Latsko

Portella

et al. 2021

Trends in Endocrinology & Metabolism

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“…Insulin receptors (IR) are expressed throughout the brain [5] (striatum, prefrontal cortex [6,7] and hippocampus [8,9]). Insulin is actively transported across the blood-brain barrier, and its action on mesocorticolimbic receptors modulates synaptic plasticity in dopaminergic neurons, affecting dopamine-related behaviors such as response to reward [10], impulsivity [11], mood [12,13], cognition [14] and decision-making [15]. Impulsivity associated with affected dopamine signaling is also a core feature of attention deficit hyperactivity disorder (ADHD), which is co-morbid with obesity [16].…”

Section: Introductionmentioning

confidence: 99%

A biologically-informed polygenic score identifies endophenotypes and clinical conditions associated with the insulin receptor function on specific brain regions

et al. 2019

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Background Activation of brain insulin receptors modulates reward sensitivity, inhibitory control and memory. Variations in the functioning of this mechanism likely associate with individual differences in the risk for related mental disorders (attention deficit hyperactivity disorder or ADHD, addiction, dementia), in agreement with the high co-morbidity between insulin resistance and psychopathology. These neurobiological mechanisms can be explored using genetic studies. We propose a novel, biologically informed genetic score reflecting the mesocorticolimbic and hippocampal insulin receptor-related gene networks, and investigate if it predicts endophenotypes (impulsivity, cognitive ability) in community samples of children, and psychopathology (addiction, dementia) in adults. Methods Lists of genes co-expressed with the insulin receptor in the mesocorticolimbic system or hippocampus were created. SNPs from these genes (post-clumping) were compiled in a polygenic score using the association betas described in a conventional GWAS (ADHD in the mesocorticolimbic score and Alzheimer in the hippocampal score). Across multiple samples ( n = 4502), the biologically informed, mesocorticolimbic or hippocampal specific insulin receptor polygenic scores were calculated, and their ability to predict impulsivity, risk for addiction, cognitive performance and presence of Alzheimer's disease was investigated. Findings The biologically-informed ePRS-IR score showed better prediction of child impulsivity and cognitive performance, as well as risk for addiction and Alzheimer's disease in comparison to conventional polygenic scores for ADHD, addiction and dementia. Interpretation This novel, biologically-informed approach enables the use of genomic datasets to probe relevant biological processes involved in neural function and disorders. Fund Toxic Stress Research network of the JPB Foundation, Jacobs Foundation (Switzerland), Sackler Foundation.

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Hippocampal insulin resistance and altered food decision-making as players on obesity risk

Cited by 14 publications

References 227 publications

Swimming Suppresses Cognitive Decline of HFD-Induced Obese Mice through Reversing Hippocampal Inflammation, Insulin Resistance, and BDNF Level

Swimming Suppresses Cognitive Decline of HFD-Induced Obese Mice through Reversing Hippocampal Inflammation, Insulin Resistance, and BDNF Level

Early adversity and insulin: neuroendocrine programming beyond glucocorticoids

A biologically-informed polygenic score identifies endophenotypes and clinical conditions associated with the insulin receptor function on specific brain regions

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