Topics

Visceral adipose NLRP3 impairs cognition in obesity via IL1R1 on Cx3cr1+ cells.

07:00 EST 14th January 2020 | BioPortfolio

Summary of "Visceral adipose NLRP3 impairs cognition in obesity via IL1R1 on Cx3cr1+ cells."

Induction of the inflammasome protein cryopyrin (NLRP3) in visceral adipose tissue (VAT) promotes release of the pro-inflammatory cytokine interleukin-1β (IL1β) in obesity. While this mechanism contributes to peripheral metabolic dysfunction, effects on the brain remain unexplored. These studies investigated whether visceral adipose NLRP3 impairs cognition by activating microglial interleukin-1 receptor 1 (IL1R1). After observing protection against obesity-induced neuroinflammation and cognitive impairment in NLRP3KO mice, we transplanted VAT from obese WT or NLRP3KO donors into lean recipients. Transplantation of VAT from a WT donor (TRANSWT) increased hippocampal IL1β and impaired cognition, but VAT transplants from comparably obese NLRP3KO donors (TRANSKO) had no effect. Visceral adipose NLRP3 was required for deficits in long-term potentiation (LTP) in transplant recipients, and LTP impairment in TRANSWT mice was IL1-dependent. Flow cytometric and gene expression analyses revealed that VAT transplantation recapitulated the effects of obesity on microglial activation and IL1β gene expression, and visualization of hippocampal microglia revealed similar effects in vivo. Inducible ablation of IL1R1 in CX3CR1-expressing cells eliminated cognitive impairment in mice with dietary obesity and in transplant recipients and restored immunoquiescence in hippocampal microglia. These results indicate that visceral adipose NLRP3 impairs memory via IL1-mediated microglial activation, and suggest that NLRP3-IL1β signaling may underlie correlations between visceral adiposity and cognitive impairment in humans.

Affiliation

Journal Details

This article was published in the following journal.

Name: The Journal of clinical investigation
ISSN: 1558-8238
Pages:

Links

DeepDyve research library

PubMed Articles [5007 Associated PubMed Articles listed on BioPortfolio]

Apigenin inhibits STAT3/CD36 signaling axis and reduces visceral obesity.

Visceral obesity is the excess deposition of visceral fat within the abdominal cavity that surrounds vital organs. Visceral obesity is directly associated with metabolic syndrome, breast cancer and en...

Overproduction of endothelin-1 impairs glucose tolerance but does not promote visceral adipose tissue inflammation or limit metabolic adaptations to exercise.

Endothelin-1 (ET-1) is a potent vasoconstrictor and proinflammatory peptide that is upregulated in obesity. Herein, we tested the hypothesis that ET-1 signaling promotes visceral adipose tissue (AT) i...

Aging-related changes in fluid intelligence, muscle and adipose mass, and sex-specific immunologic mediation: a longitudinal UK Biobank study.

Obesity in midlife and early late-life is associated with worse normal cognitive aging. Dual-energy x-ray absorptiometry (DEXA) suggests that visceral adipose mass (VAM) plays a predominant role, wher...

Impact of abdominal fat distribution, visceral fat, and subcutaneous fat on coronary plaque scores assessed by 320-row computed tomography coronary angiography.

Obesity is a risk factor for coronary artery disease (CAD), but the association between fat distribution, i.e., visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and coronary artery...

Visceral adipose tissue volume is associated with premature atherosclerosis in early type 2 diabetes mellitus independent of traditional risk factors.

Type 2 diabetes mellitus (T2DM) is commonly associated with abdominal obesity, predominantly with high visceral adipose tissue (VAT), and is accompanied by premature atherosclerosis. However, the asso...

Clinical Trials [5187 Associated Clinical Trials listed on BioPortfolio]

Endocrine Regulation of Lipolysis in Obesity and Diabetes

Adipose tissue (AT) dysfunction is a commonly observed feature of metabolic dysfunction in obesity and diabetes. An important characteristic when examining AT function is the capacity to b...

Description of the Endothelial Phenotypes From the Subcutaneous Abdominal and Gluteo-femoral Adipose Tissues in Women

The endothelium is a key barrier between blood and tissue compartments. It is a major target of factors involved in metabolic and cardiovascular pathologies. However, the study of native h...

Central Obesity in Cases of OAB

Obesity is not a homogeneous condition and that the regional distribution of adipose tissue is important to understanding the relation of obesity to disturbances in glucose and lipid metab...

Visceral Adiposity and Diabetes: Translating Form to Function Using Imaging

This study is a clinical study to investigate the gluconeogenesis pathway related to visceral adipose tissue (VAT) in obese individuals without type 2 diabetes and the effects of empaglifl...

mTOR and Adipose Tissue Inflammation

The target of rapamycin complex 2 (TORC2) is an evolutionarily conserved serine/threonine protein kinase that controls growth and metabolism. In mammals (including humans), mammalian TOR c...

Medical and Biotech [MESH] Definitions

Fatty tissue inside the ABDOMINAL CAVITY, including visceral fat and retroperitoneal fat. It is the most metabolically active fat in the body and easily accessible for LIPOLYSIS. Increased visceral fat is associated with metabolic complications of OBESITY.

Brown fat-like adipose tissue that develops in WHITE ADIPOSE TISSUE from non-MYOGENIC REGULATORY FACTOR 5 expressing cell lineage.

A condition of having excess fat in the abdomen. Abdominal obesity is typically defined as waist circumferences of 40 inches or more in men and 35 inches or more in women. Abdominal obesity raises the risk of developing disorders, such as diabetes, hypertension and METABOLIC SYNDROME X.

Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.

A 30-kDa COMPLEMENT C1Q-related protein, the most abundant gene product secreted by FAT CELLS of the white ADIPOSE TISSUE. Adiponectin modulates several physiological processes, such as metabolism of GLUCOSE and FATTY ACIDS, and immune responses. Decreased plasma adiponectin levels are associated with INSULIN RESISTANCE; TYPE 2 DIABETES MELLITUS; OBESITY; and ATHEROSCLEROSIS.

Quick Search


DeepDyve research library

Relevant Topics

Obesity
Obesity is the condition in which excess fat has accumulated in the body (mostly in subcutaneous tissues). clinical obesity is considered to be present when a person has a BMI of over 30 (Oxford Dictionary of Medicine). It is becoming increasing common i...

Nutrition
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Cytokine
Cytokines include chemokines, lymphokines, and monokines. Cells of the immune system communicate with one another by releasing and responding to chemical messengers called cytokines. These proteins are secreted by immune cells and act on other cells to...


Searches Linking to this Article