IRE1 gives weight to obesity-associated inflammation

Bujisic, Bojan; Martinon, Fabio

doi:10.1038/ni.3725

Cited by 20 publications

(18 citation statements)

References 11 publications

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“…found that IRE1α was activated in adipose tissue macrophages and adipocytes of HFD fed mice (172). Their observations are consistent with other studies showing that in genetic and diet-induced models of obesity, IRE1α undergoes prominent activation (173).…”

Section: Loss Of Proteostasissupporting

confidence: 93%

Obesity May Accelerate the Aging Process

2019

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Lines of evidence from several studies have shown that increases in life expectancy are now accompanied by increased disability rate. The expanded lifespan of the aging population imposes a challenge on the continuous increase of chronic disease. The prevalence of overweight and obesity is increasing at an alarming rate in many parts of the world. Further to increasing the onset of metabolic imbalances, obesity leads to reduced life span and affects cellular and molecular processes in a fashion resembling aging. Nine key hallmarks of the aging process have been proposed. In this review, we will review these hallmarks and discuss pathophysiological changes that occur with obesity, that are similar to or contribute to those that occur during aging. We present and discuss the idea that obesity, in addition to having disease-specific effects, may accelerate the rate of aging affecting all aspects of physiology and thus shortening life span and health span.

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Section: Loss Of Proteostasissupporting

confidence: 93%

Obesity May Accelerate the Aging Process

2019

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“…A recently described example is the Inositol Requiring Enzyme-1 (IRE-1), an endoplasmic reticular enzyme which responds to imposed cellular stress and high fat content feeding by contributing to activation of the Unfolded Protein Response, a co-ordinated reaction to stress which can lead to macromolecular degradation and apoptosis. It has been shown that in adipose tissue-resident macrophages IRE1α activation induces a shift in the biomolecular profile of those cells towards a more highly pro-inflammatory (M1) state of polarization ( Bujisic and Martinon, 2017 ; Shan et al, 2017 ). If this activation is maintained chronically, it could well contribute to the initiation of tumor formation.…”

Section: Obesity and Cancermentioning

confidence: 99%

Obesity and Cancer: Existing and New Hypotheses for a Causal Connection

2018

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Existing explanations of obesity-associated cancer emphasise direct mutagenic effects of dietary components or hormonal imbalance. Some of these hypotheses are reviewed briefly, but recent evidence suggests a major role for chronic inflammation in cancer risk, possibly involving dietary content. These ideas include the inflammation-induced activation of the kynurenine pathway and its role in feeding and metabolism by activation of the aryl hydrocarbon receptor (AHR) and by modulating synaptic transmission in the brain. Evidence for a role of the kynurenine pathway in carcinogenesis then provides a potentially major link between obesity and cancer. A second new hypothesis is based on evidence that serine proteases can deplete cells of the tumour suppressors Deleted in Colorectal Cancer (DCC) and neogenin. These enzymes include mammalian chymotryptic proteases released by pro-inflammatory neutrophils and macrophages. Blood levels of chymotrypsin itself increase in parallel with food intake. The mechanistically similar bacterial enzyme subtilisin is widespread in the environment, animal probiotics, meat processing and cleaning products. Simple public health schemes in these areas, with selective serine protease inhibitors and AHR antagonists and could prevent a range of intestinal and other cancers.

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“…This molecular mechanism may link ER stress with insulin resistance. The role for IRE1α in ATMs in suppressing the alternative M2 polarization of macrophages and hence impairing adaptive thermogenesis, builds the connection between ER stress, macrophage polarization and energy homeostasis (Bujisic & Martinon, 2017). Thus, macrophages have a dual role, changing their status to support immune responses, obesity development and related diseases (Herrero, Marques, Lloberas, & Celada, 2001).…”

Section: Transcription Factors For Tissue-resident Macrophage Develmentioning

confidence: 99%

The origins and homeostasis of monocytes and tissue‐resident macrophages in physiological situation

Zhao

Zou

Du³

et al. 2018

Journal Cellular Physiology

128

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Monocytes and macrophages are critical effectors and regulators of innate immune response. They not only play crucial and distinctive roles in homeostasis, but also contribute to some pathologic processes. The heterogeneity of the macrophage lineage has been widely recognized and, in part, is a result of the specialization of resident macrophages in particular tissue microenvironments. Monocytes are usually known to originate in the bone marrow from a common myeloid progenitor that is shared with neutrophils, and they are then released into the peripheral blood. However, the origin of tissue-resident macrophages, crucial for homeostasis and immunity, has remained controversial until recently. During embryonic organogenesis, macrophages derived from yolk sac and fetal liver precursors are seeded throughout tissues, persisting in the adulthood as resident, self-maintaining populations. After birth, bone marrow-derived monocytes can replenish tissue resident macrophages following injury, infection and inflammation. In this review, we will mainly summarize our current understanding on the origin, ontogeny and fates of tissue macrophages and will briefly discuss the molecular regulation of resident macrophage homeostasis in physiological situation.

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IRE1 gives weight to obesity-associated inflammation

Cited by 20 publications

References 11 publications

Obesity May Accelerate the Aging Process

Obesity May Accelerate the Aging Process

Obesity and Cancer: Existing and New Hypotheses for a Causal Connection

The origins and homeostasis of monocytes and tissue‐resident macrophages in physiological situation

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