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Open AccessJournal ArticleDOI

Nutrient sensing and inflammation in metabolic diseases.

Gökhan S. Hotamisligil, +1 more
- 01 Dec 2008 - 
- Vol. 8, Iss: 12, pp 923-934
TLDR
This Review provides an overview of several important networks that sense and manage nutrients and discusses how they integrate with immune and inflammatory pathways to influence the physiological and pathological metabolic states in the body.
Abstract
The proper functioning of the pathways that are involved in the sensing and management of nutrients is central to metabolic homeostasis and is therefore among the most fundamental requirements for survival. Metabolic systems are integrated with pathogen-sensing and immune responses, and these pathways are evolutionarily conserved. This close functional and molecular integration of the immune and metabolic systems is emerging as a crucial homeostatic mechanism, the dysfunction of which underlies many chronic metabolic diseases, including type 2 diabetes and atherosclerosis. In this Review we provide an overview of several important networks that sense and manage nutrients and discuss how they integrate with immune and inflammatory pathways to influence the physiological and pathological metabolic states in the body.

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Citations
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Journal ArticleDOI

Inflammageing and metaflammation: The yin and yang of type 2 diabetes.

TL;DR: A plethora of pathological cascades triggered by gluco- and lipotoxicity are dissected, converging on candidate phenomena possibly explaining the enduring pro-inflammatory program observed in diabetic tissues, i.e. persistent immune-system stimulation, accumulation of senescent cells, epigenetic rearrangements, and alterations in microbiota composition.
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Related actions of probiotics and antibiotics on gut microbiota and weight modification

TL;DR: The effects of probiotics and antibiotics on the gut microbiota of human beings and animals are presented and their potential therapeutic use as interventions for weight gain and loss in human beings are discussed.
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Epigenetic Regulation of Macrophage Polarization by DNA Methyltransferase 3b

TL;DR: It is found that the expression of DNMT3b was significantly induced in macrophages exposed to the saturated fatty acid stearate, was higher in ATMs isolated from obese mice, but was significantly lower in alternatively activated M2 vs classically activated M1 ATMs, suggesting a role for DN MT3b in regulation of macrophage polarization and inflammation in obesity.
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Recent Insights into the Role of Unfolded Protein Response in ER Stress in Health and Disease

TL;DR: Current concepts and mechanisms of UPR as studied in different cells and model systems are reviewed and the relevance of U PR and related stress signals in various human diseases is highlighted.
Journal ArticleDOI

Type 2 diabetes as a disease of ectopic fat

TL;DR: Obesity is the major risk factor for T2DM and appears to drive tissue insulin resistance in part via gain of ectopic fat, with the best-studied organ being the liver, but ectopicfat in the pancreas may contribute to β-cell dysfunction.
References
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Journal ArticleDOI

An obesity-associated gut microbiome with increased capacity for energy harvest

TL;DR: It is demonstrated through metagenomic and biochemical analyses that changes in the relative abundance of the Bacteroidetes and Firmicutes affect the metabolic potential of the mouse gut microbiota and indicates that the obese microbiome has an increased capacity to harvest energy from the diet.
Journal ArticleDOI

Inflammation and metabolic disorders

TL;DR: Dysfunction of the immune response and metabolic regulation interface can be viewed as a central homeostatic mechanism, dysfunction of which can lead to a cluster of chronic metabolic disorders, particularly obesity, type 2 diabetes and cardiovascular disease.
Journal ArticleDOI

Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance

TL;DR: A role for TNF-alpha in obesity and particularly in the insulin resistance and diabetes that often accompany obesity is indicated.
Journal ArticleDOI

Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.

TL;DR: It is proposed that obesity-related insulin resistance is, at least in part, a chronic inflammatory disease initiated in adipose tissue, and that macrophage-related inflammatory activities may contribute to the pathogenesis of obesity-induced insulin resistance.
Journal ArticleDOI

Signal integration in the endoplasmic reticulum unfolded protein response

TL;DR: Together, at least three mechanistically distinct arms of the UPR regulate the expression of numerous genes that function within the secretory pathway but also affect broad aspects of cell fate and the metabolism of proteins, amino acids and lipids.
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