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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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Type 2 diabetes as an inflammatory disease.

TL;DR: Preliminary results from clinical trials with salicylates and interleukin-1 antagonists support the notion that inflammation participates in the pathogenesis of type 2 diabetes and have opened the door for immunomodulatory strategies for the treatment of T2D that simultaneously lower blood glucose levels and potentially reduce the severity and prevalence of the associated complications of this disease.
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The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance

TL;DR: It is established that calorie restriction and exercise-mediated weight loss in obese individuals with type 2 diabetes is associated with a reduction in adipose tissue expression of Nlrp3 as well as with decreased inflammation and improved insulin sensitivity, and that the NlrP3 inflammasome senses obesity-associated danger signals and contributes to obesity-induced inflammation and insulin resistance.
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Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis†

TL;DR: Endoplasmic reticulum stress and related signaling networks, (adipo)cytokines, and innate immunity are emerging as central pathways that regulate key features of NASH.
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Metabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor 5

TL;DR: Results support the emerging view that the gut microbiota contributes to metabolic disease and suggest that malfunction of the innate immune system may promote the development of metabolic syndrome.
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NF-κB, inflammation, and metabolic disease.

TL;DR: It is now widely appreciated that chronic low-grade inflammation plays a key role in the initiation, propagation, and development of metabolic diseases, and numerous recent studies have implicated the transcription factor NF-κB in the development of such diseases, thereby further establishing inflammation as a critical factor in their etiology.
References
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Vesicular Stomatitis Virus Infection Alters the eIF4F Translation Initiation Complex and Causes Dephosphorylation of the eIF4E Binding Protein 4E-BP1

TL;DR: Data show that VSV infection results in modifications of the eIF4F complex that are correlated with the inhibition of host protein synthesis and that translation of VSV mRNAs occurs despite lowered concentrations of the active cap-binding eIF 4F complex.
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TL;DR: Structural features that underlie the nucleocytoplasmic transport of FABP4 support the validity of the "pre-existing equilibrium" model for the ligand-controlled activation of the nuclear import of F ABP4 and provide insight into the fundamental question of how proteins are activated by ligands.
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The Structure of Mononuclear Phagocytes Differentiating In Vivo: I. Sequential Fine and Histologic Studies of the Effect of Bacillus Calmette-Guerin (BCG)

TL;DR: The observations demonstrate directly the differentiation of mononuclear phagocytes in vivo and suggest some, if not all, characteristic features of granulomatous inflammation result from such differentiation.
Journal ArticleDOI

Reductions in total body fat decrease humoral immunity.

TL;DR: The results suggest that reductions in energy availability can impair humoral immunity in seasonally breeding rodent species, prairie voles and Siberian hamsters.
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