Icons / Logo / Facebook Created with Sketch. Icons / Logo / Google Created with Sketch. Icons / Logo / ORCID Created with Sketch. Branding/Logomark minus Citation Combined Shape Icon/Bookmark-empty Icon/Copy Icon/Collection Icon/Close Copy 7 no author result Created with Sketch. Icon/Back Created with Sketch. Match!

Virus-Induced Interferon-γ Causes Insulin Resistance in Skeletal Muscle and Derails Glycemic Control in Obesity

Published on Jul 1, 2018in Immunity 21.52
· DOI :10.1016/j.immuni.2018.05.005
Marko Šestan4
Estimated H-index: 4
(University of Rijeka),
Sonja Marinović2
Estimated H-index: 2
(University of Rijeka)
+ 8 AuthorsBojan Polić26
Estimated H-index: 26
(University of Rijeka)
Cite
Abstract
Summary Pro-inflammatory cytokines of a T helper-1-signature are known to promote insulin resistance (IR) in obesity, but the physiological role of this mechanism is unclear. It is also unknown whether and how viral infection induces loss of glycemic control in subjects at risk for developing diabetes mellitus type 2 (DM2). We have found in mice and humans that viral infection caused short-term systemic IR. Virally-induced interferon-γ (IFN-γ) directly targeted skeletal muscle to downregulate the insulin receptor but did not cause loss of glycemic control because of a compensatory increase of insulin production. Hyperinsulinemia enhanced antiviral immunity through direct stimulation of CD8 + effector T cell function. In pre-diabetic mice with hepatic IR caused by diet-induced obesity, infection resulted in loss of glycemic control. Thus, upon pathogen encounter, the immune system transiently reduces insulin sensitivity of skeletal muscle to induce hyperinsulinemia and promote antiviral immunity, which derails to glucose intolerance in pre-diabetic obese subjects. Video Abstract
  • References (67)
  • Citations (5)
Cite
References67
Newest
Published on Nov 1, 2017in Immunity 21.52
Elise Dalmas7
Estimated H-index: 7
(University of Basel),
Frank M. Lehmann2
Estimated H-index: 2
(University of Basel)
+ 18 AuthorsDianne H. Dapito2
Estimated H-index: 2
(ETH Zurich)
Summary Pancreatic-islet inflammation contributes to the failure of β cell insulin secretion during obesity and type 2 diabetes. However, little is known about the nature and function of resident immune cells in this context or in homeostasis. Here we show that interleukin (IL)-33 was produced by islet mesenchymal cells and enhanced by a diabetes milieu (glucose, IL-1β, and palmitate). IL-33 promoted β cell function through islet-resident group 2 innate lymphoid cells (ILC2s) that elicited retin...
Published on Jun 1, 2017in Cell Reports 7.82
Christoph Hirche2
Estimated H-index: 2
(MHH: Hannover Medical School),
Theresa Frenz10
Estimated H-index: 10
(MHH: Hannover Medical School)
+ 15 AuthorsChintan Chhatbar5
Estimated H-index: 5
(MHH: Hannover Medical School)
Summary Quiescent long-term hematopoietic stem cells (LT-HSCs) are efficiently activated by type I interferon (IFN-I). However, this effect remains poorly investigated in the context of IFN-I-inducing virus infections. Here we report that both vesicular stomatitis virus (VSV) and murine cytomegalovirus (MCMV) infection induce LT-HSC activation that substantially differs from the effects triggered upon injection of synthetic IFN-I-inducing agents. In both infections, inflammatory responses had to...
Published on Mar 1, 2017in Nature Immunology 23.53
Erez Dror7
Estimated H-index: 7
,
Elise Dalmas7
Estimated H-index: 7
+ 17 AuthorsFriederike Schulze4
Estimated H-index: 4
The deleterious effect of chronic activation of the IL-1β system on type 2 diabetes and other metabolic diseases is well documented. However, a possible physiological role for IL-1β in glucose metabolism has remained unexplored. Here we found that feeding induced a physiological increase in the number of peritoneal macrophages that secreted IL-1β, in a glucose-dependent manner. Subsequently, IL-1β contributed to the postprandial stimulation of insulin secretion. Accordingly, lack of endogenous I...
Published on Sep 1, 2016in Nature Reviews Immunology 44.02
Luke A. J. O'Neill93
Estimated H-index: 93
,
Rigel J. Kishton13
Estimated H-index: 13
,
Jeffrey C. Rathmell59
Estimated H-index: 59
Immunometabolism is emerging an important area of immunological research, but for many immunologists the complexity of the field can be daunting. Here, the authors provide an overview of six key metabolic pathways that occur in immune cells and explain what is known (and what is still to be uncovered) concerning their effects on immune cell function.
Published on Sep 1, 2016in Cell 36.22
Andrew Wang12
Estimated H-index: 12
(Yale University),
Sarah C. Huen11
Estimated H-index: 11
(Yale University)
+ 5 AuthorsRuslan Medzhitov100
Estimated H-index: 100
(Yale University)
Summary Acute infections are associated with a set of stereotypic behavioral responses, including anorexia, lethargy, and social withdrawal. Although these so-called sickness behaviors are the most common and familiar symptoms of infections, their roles in host defense are largely unknown. Here, we investigated the role of anorexia in models of bacterial and viral infections. We found that anorexia was protective while nutritional supplementation was detrimental in bacterial sepsis. Furthermore,...
Published on Apr 1, 2016in Cell 36.22
Daniel Okin6
Estimated H-index: 6
(Yale University),
Ruslan Medzhitov100
Estimated H-index: 100
(Yale University)
Control of plasma glucose level is essential to organismal survival. Sustained inflammation has been implicated in control of glucose homeostasis in cases of infection, obesity, and type 2 diabetes; however, the precise role of inflammation in these complex disease states remains poorly understood. Here, we find that sustained inflammation results in elevated plasma glucose due to increased hepatic glucose production. We find that sustained inflammation suppresses CYP7A1, leading to accumulation...
Published on Oct 1, 2015in Cytokine 3.08
Dov B. Ballak4
Estimated H-index: 4
(Radboud University Nijmegen),
Rinke Stienstra29
Estimated H-index: 29
(Radboud University Nijmegen)
+ 2 AuthorsJ.A. van Diepen2
Estimated H-index: 2
(Radboud University Nijmegen)
Obesity is characterized by a chronic, low-grade inflammation that contributes to the development of insulin resistance and type 2 diabetes. Cytokines and chemokines produced by immunocompetent cells influence local as well as systemic inflammation and are therefore critical contributors to the pathogenesis of type 2 diabetes. Hence, cytokines that modulate inflammatory responses are emerging as potential targets for intervention and treatment of the metabolic consequences of obesity. The interl...
Published on Sep 1, 2015in European Journal of Immunology 4.70
Felix M. Wensveen18
Estimated H-index: 18
(University of Rijeka),
Sonja Valentić3
Estimated H-index: 3
(University of Rijeka)
+ 2 AuthorsBojan Polić26
Estimated H-index: 26
(University of Rijeka)
Obesity is associated with the accumulation of pro-inflammatory cells in visceral adipose tissue (VAT), which is an important underlying cause of insulin resistance and progression to diabetes mellitus type 2 (DM2). Although the role of pro-inflammatory cytokines in disease development is established, the initiating events leading to immune cell activation remain elusive. Lean adipose tissue is predominantly populated with regulatory cells, such as eosinophils and type 2 innate lymphocytes. Thes...
Published on Apr 1, 2015in Nature Immunology 23.53
Felix M. Wensveen18
Estimated H-index: 18
(University of Rijeka),
Vedrana Jelenčić5
Estimated H-index: 5
(University of Rijeka)
+ 10 AuthorsF. Thomas Wunderlich19
Estimated H-index: 19
(MPG: Max Planck Society)
Visceral adipose tissue (VAT) inflammation drives obesity-induced insulin resistance. Polic and colleagues show that VAT NK cells sense obesity-induced adipose tissue stress and drive inflammation through the production of interferon-γ.
Published on Apr 1, 2015in Laboratory Animals 1.12
Jana C. Mossanen9
Estimated H-index: 9
(RWTH Aachen University),
Frank Tacke61
Estimated H-index: 61
(RWTH Aachen University)
The induction of acute hepatic damage by acetaminophen (N-acetyl-p-aminophenol [APAP]), also termed paracetamol, is one of the most commonly used experimental models of acute liver injury in mice. The specific values of this model are the highly reproducible, dose-dependent hepatotoxicity of APAP and its outstanding translational importance, because acetaminophen overdose is one of the most frequent reasons for acute liver failure (ALF) in humans. However, preparation of concentrated APAP workin...
Cited By5
Newest
Published on Jul 1, 2019in Molecular metabolism 6.18
Guo Xiaolong (CQMU: Chongqing Medical University), Zhang Zhichun (CQMU: Chongqing Medical University)+ 10 AuthorsTao Linfen (CQMU: Chongqing Medical University)
Abstract Objective Brown and beige adipocytes in humans and rodents are specialized to burn lipids for heat generation as a natural defense against cold and obesity, which is advantageous to metabolic homeostasis. MicroRNAs as another regulatory layer to regulate metabolic homeostasis attracted a lot of attentions. Our previous work revealed microRNA (miR)-203 as a brown adipocyte-enriched microRNA involved in brown adipocytes development. However, the potential role of miR-203 in adipose tissue...
Published on Jun 20, 2019in PLOS Pathogens 6.46
Nico A. Contreras2
Estimated H-index: 2
(UA: University of Arizona),
Katarzyna Sitnik7
Estimated H-index: 7
+ 3 AuthorsJanko Nikolich-Žugich17
Estimated H-index: 17
(UA: University of Arizona)
Cytomegalovirus (CMV) is a ubiquitous herpesvirus infecting most of the world’s population. CMV has been rigorously investigated for its impact on lifelong immunity and potential complications arising from lifelong infection. A rigorous adaptive immune response mounts during progression of CMV infection from acute to latent states. CD8 T cells, in large part, drive this response and have very clearly been demonstrated to take up residence in the salivary gland and lungs of infected mice during l...
Published on Jun 18, 2019in Obesity Surgery 3.60
Hideya Kashihara10
Estimated H-index: 10
(University of Tokushima),
Mitsuo Shimada63
Estimated H-index: 63
(University of Tokushima)
+ 5 AuthorsChie Takasu11
Estimated H-index: 11
(University of Tokushima)
Background The aim of this study was to investigate gut inflammation and permeability in rats after duodenal-jejunal bypass (DJB) and in rats injected with a glucagon-like peptide-1 (GLP-1) receptor analog.
Published on Jun 1, 2019in Journal of Investigative Dermatology 6.29
K. Ikumi1
Estimated H-index: 1
(Nagoya City University),
Mizuyu Odanaka1
Estimated H-index: 1
(Nagoya City University)
+ 8 AuthorsAkimichi Morita33
Estimated H-index: 33
(Nagoya City University)
Chronic low-grade inflammation can cause several metabolic syndromes. Patients with psoriasis, a chronic immunological skin inflammation, often develop diabetes. However, it is not clear to date how psoriasis leads to, or is correlated with, glucose intolerance. Here, we investigate whether psoriasis itself is correlated with hyperglycemia in humans and mice. In patients, the severity of psoriasis was correlated with high blood glucose levels, and treatment of psoriasis by phototherapy improved ...
Published on May 1, 2019in Current Diabetes Reports 4.00
Fabrizia Bonacina7
Estimated H-index: 7
(University of Milan),
Andrea Baragetti12
Estimated H-index: 12
(University of Milan)
+ 1 AuthorsGiuseppe Danilo Norata41
Estimated H-index: 41
(University of Milan)
Purpose of Review Metabolic reprogramming is increasingly recognized as an essential trait of functional activation of immune cells. Here, we describe the link between immuno-metabolism, diabetes, and diabetic nephropathy.
Published on May 1, 2019in Trends in Endocrinology and Metabolism 9.78
Christian Herder62
Estimated H-index: 62
,
Michael Roden66
Estimated H-index: 66
(HHU: University of Düsseldorf),
Dan Ziegler49
Estimated H-index: 49
The most prevalent chronic complications of diabetes are diabetic neuropathies, among which distal sensorimotor polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) are the best studied. Their major clinical sequelae such as foot ulcers, neuropathic pain, and orthostatic hypotension are associated with lower quality of life and increased risk of mortality. Here we discuss the recent insights into DSPN and CAN focusing on two prospective cohorts; that is, the German Diabetes Study ...
Published on Oct 1, 2018in Nature Reviews Endocrinology 24.65
Christian Herder62
Estimated H-index: 62
(HHU: University of Düsseldorf)
Viral infections induce muscle insulin resistance in mice through the stimulation of IFNγ. This results in increased insulin levels, which promote antiviral CD8+ T cell activation. In obese mice, insulin resistance triggered by IFNγ also leads to deterioration of glycaemic control. These findings highlight the intricate link between the immune system and metabolic regulation.
Published on Jul 1, 2018in Immunity 21.52
Kaitlin Kiernan1
Estimated H-index: 1
(Duke University),
Nancie J. MacIver13
Estimated H-index: 13
(Duke University)
In this issue of Immunity , Sestan et al. (2018) show that viral-induced inflammation leads to insulin resistance in skeletal muscle, followed by compensatory hyperinsulinemia, which promotes the anti-viral effector response of CD8 + T cells. Interestingly, this leads to persistent glucose intolerance and the progression of type 2 diabetes in pre-diabetic animals.