Nutrient sensing and inflammation in metabolic diseases.
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.read more
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
Bolormaa Vandanmagsar,Yun-Hee Youm,Anthony Ravussin,Jose E. Galgani,Krisztian Stadler,Randall L. Mynatt,Eric Ravussin,Jacqueline M. Stephens,Vishwa Deep Dixit +8 more
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
Matam Vijay-Kumar,Jesse D. Aitken,Frederic A. Carvalho,Tyler C. Cullender,Simon M. Mwangi,Shanthi Srinivasan,Shanthi V. Sitaraman,Rob Knight,Ruth E. Ley,Andrew T. Gewirtz +9 more
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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Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity
Sung Hee Um,Francesca Frigerio,Mitsuhiro Watanabe,Frédéric Picard,Manel Joaquin,Melanie Sticker,Stefano Fumagalli,Peter R. Allegrini,Sara C. Kozma,Sara C. Kozma,Johan Auwerx,George Thomas +11 more
TL;DR: It is reported that S6K1-deficient mice are protected against obesity owing to enhanced β-oxidation, however on a high fat diet, levels of glucose and free fatty acids still rise in S6k1- deficient mice, resulting in insulin receptor desensitization.
Journal Article
Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. [Erratum: 2004 Sept. 23, v. 431, no. 7007, p. 485.]
Sung Hee Um,Francesca Frigerio,Mitsuhiro Watanabe,Frédéric Picard,Manel Joaquin,Melanie Sticker,Stefano Fumagalli,Peter R. Allegrini,Sara C. Kozma,Johan Auwerx +9 more
TL;DR: In this article, S6K1-deficient mice are protected against obesity owing to enhanced β-oxidation, but on a high fat diet, levels of glucose and free fatty acids still rise in S6k1-dependent mice, resulting in insulin receptor desensitization.
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Translational Control Is Required for the Unfolded Protein Response and In Vivo Glucose Homeostasis
Donalyn Scheuner,Benbo Song,Edward L. McEwen,Chuan Liu,Ross Laybutt,Patrick J. Gillespie,Thom Saunders,Susan Bonner-Weir,Randal J. Kaufman +8 more
TL;DR: It is demonstrated that regulation of translation through eIF2alpha phosphorylation is essential for the ER stress response and in vivo glucose homeostasis.
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Hypothalamic IKKβ/NF-κB and ER Stress Link Overnutrition to Energy Imbalance and Obesity
TL;DR: The results show that the hypothalamic IKKbeta/NF-kappaB program is a general neural mechanism for energy imbalance underlying obesity and suggest that suppression of IKK beta either broadly across the brain or locally within the mediobasal hypothalamus, or specifically in hypothalamic AGRP neurons significantly protects against obesity and glucose intolerance.
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Diabetes Mellitus and Exocrine Pancreatic Dysfunction in Perk−/− Mice Reveals a Role for Translational Control in Secretory Cell Survival
Heather P. Harding,Huiqing Zeng,Yuhong Zhang,Rivka Jungries,Peter Chung,Heidi Plesken,David D. Sabatini,David Ron +7 more
TL;DR: Findings suggest a special role for translational control in protecting secretory cells from ER stress in diabetes mellitus and exocrine pancreatic insufficiency.