FGF21 Attenuates High-Fat Diet-Induced Cognitive Impairment via Metabolic Regulation and Anti-inflammation of Obese Mice

Accumulating studies suggest that overnutrition-associated obesity may lead to development of type 2 diabetes mellitus and metabolic syndromes (MetS). MetS and its components are important risk factors of mild cognitive impairment, age-related cognitive decline, vascular dementia, and Alzheimer’s di...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	Molecular neurobiology Ročník 55; číslo 6; s. 4702 - 4717
Hlavní autoři:	Wang, Qingzhi, Yuan, Jing, Yu, Zhanyang, Lin, Li, Jiang, Yinghua, Cao, Zeyuan, Zhuang, Pengwei, Whalen, Michael J., Song, Bo, Wang, Xiao-Jie, Li, Xiaokun, Lo, Eng H., Xu, Yuming, Wang, Xiaoying
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Springer US 01.06.2018 Springer Nature B.V
Témata:	Age Animals Anti-Inflammatory Agents - pharmacology Anti-Inflammatory Agents - therapeutic use Anxiety Anxiety - complications Anxiety - drug therapy Behavior, Animal Biomedical and Life Sciences Biomedicine Blood-Brain Barrier - drug effects Blood-Brain Barrier - pathology Cell Biology Clinical significance Cognitive ability Cognitive Dysfunction - complications Cognitive Dysfunction - drug therapy Cognitive Dysfunction - metabolism Cognitive Dysfunction - pathology Cytokines - metabolism Dementia disorders Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diet, High-Fat Fibroblast growth factors Fibroblast Growth Factors - pharmacology Fibroblast Growth Factors - therapeutic use Glucose - metabolism Glucose tolerance High fat diet Hippocampus Hippocampus - metabolism Humans Hyperlipidemia Hyperlipidemias - complications Hyperlipidemias - drug therapy Inflammation Inflammation - complications Inflammation - drug therapy Insulin Insulin Resistance Male Metabolic disorders Metabolism Mice, Inbred C57BL Mice, Obese Microglia - drug effects Microglia - metabolism Microglia - pathology Neurobiology Neurogenesis Neurogenesis - drug effects Neurology Neuronal Plasticity - drug effects Neurosciences Obesity Overnutrition Receptors, Fibroblast Growth Factor - metabolism Recombinant Proteins - pharmacology Recombinant Proteins - therapeutic use Risk factors Rodents Signal Transduction Vascular dementia Fibroblast growth factor 21 Inflammation Obese mice High-fat diet Metabolic disorders Cognitive impairment
ISSN:	0893-7648, 1559-1182, 1559-1182
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	Accumulating studies suggest that overnutrition-associated obesity may lead to development of type 2 diabetes mellitus and metabolic syndromes (MetS). MetS and its components are important risk factors of mild cognitive impairment, age-related cognitive decline, vascular dementia, and Alzheimer’s disease. It has been recently proposed that development of a disease-course modification strategy toward early and effective risk factor management would be clinically significant in reducing the risk of metabolic disorder-initiated cognitive decline. In the present study, we propose that fibroblast growth factor 21 (FGF21) is a novel candidate for the disease-course modification approach. Using a high-fat diet (HFD) consumption-induced obese mouse model, we tested our hypothesis that recombinant human FGF21 (rFGF21) administration is effective for improving obesity-induced cognitive dysfunction and anxiety-like behavior, by its multiple metabolic modulation and anti-pro-inflammation actions. Our experimental findings support our hypothesis that rFGF21 is protective to HFD-induced cognitive impairment, at least in part by metabolic regulation in glucose tolerance impairment, insulin resistance, and hyperlipidemia; potent systemic pro-inflammation inhibition; and improvement of hippocampal dysfunction, particularly by inhibiting pro-neuroinflammation and neurogenesis deficit. This study suggests that FGF21 might be a novel molecular target of the disease-course-modifying strategy for early intervention of MstS-associated cognitive decline.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0893-7648 1559-1182 1559-1182
DOI:	10.1007/s12035-017-0663-7