Pathways in Microbe-Induced Obesity

Cox, Laura M.; Blaser, Martin J.

doi:10.1016/j.cmet.2013.05.004

Cited by 246 publications

(193 citation statements)

References 99 publications

(134 reference statements)

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“…SCFAs, which are end-products of bacterial fermentation, account for up to 10% of caloric intake and represent an important energy source. SCFAs are known to stimulate de novo synthesis of triglycerides in the liver in part via binding to the GPCRs GPR41 (also known as FFAR3) and GPR43 (also known as FFAR2) (30,31 (16), which may account for the difference in bacterial fermentation. However, the mechanism by which intestinal FXR modulates the microbiota is not clear.…”

Section: Discussionmentioning

confidence: 99%

Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease

Jiang¹,

Xie²,

Li³

et al. 2014

J. Clin. Invest.

543

513

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. measured for 8 days. The feces were collected every 2 days for 8 days. Ileal and fecal lipids were extracted as described in the Supplemental Methods. Triglycerides were measured with a triglyceride colorimetric assay kit (Bioassay Systems). Free fatty acids (FFAs) were measured using reagents from Wako.Statistics. Experimental values are presented as the mean ± SD. Statistical analyses were performed using the 2-tailed Student's t test and 1-way ANOVA with Tukey's confirmation. Weighted UniFrac analysis to assess changes in bacterial abundance was performed on the Galaxy web-based platform. Statistical models including PCA, PLS-DA, and OPLS-DA were established to represent the major latent variables in the data matrix. P values of less than 0.05 were considered significant. Study approval. All animal studies were performed in accordance with the Institute of Laboratory Animal Resources guidelines and approved by the IACUC of the NCI.

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Section: Discussionmentioning

confidence: 99%

Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease

Jiang¹,

Xie²,

Li³

et al. 2014

J. Clin. Invest.

543

513

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“…While the past several decades have seen marked changes in diet, it is also likely that improvements in hygiene, the development of antibiotics, and widespread vaccination have resulted in significant changes in the intestinal microbiota (121,122). This raises the possibility that altered regulation of cytokines as a consequence of changes in diet, metabolism, and commensal microbes, particularly in the intestinal microenvironment, may contribute to the increased incidence of autoimmune diseases, especially those involving the IL-23/IL-17 axis (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

“…It is also important to note that the development of atherosclerosis is accelerated in several systemic human autoimmune diseases, particularly RA (120). It is thus intriguing to speculate that there are similar pathobiologic processes in play for both autoimmunity and metabolic diseases with an inflammatory component, such as type 2 diabetes and atherosclerosis.While the past several decades have seen marked changes in diet, it is also likely that improvements in hygiene, the development of antibiotics, and widespread vaccination have resulted in significant changes in the intestinal microbiota (121,122). This raises the possibility that altered regulation of cytokines as a consequence of changes in diet, metabolism, and commensal microbes, particularly in the intestinal microenvironment, may contribute to the increased incidence of autoimmune diseases, especially those involving the IL-23/IL-17 axis (Figure 3).…”

mentioning

confidence: 99%

Pouring fuel on the fire: Th17 cells, the environment, and autoimmunity

Burkett¹,

Hörste²,

Kuchroo³

2015

J. Clin. Invest.

197

137

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R e v i e w S e R i e S : A u t o i m m u n i t y2 2 1 2 jci.org Volume 125 Number 6 June 2015Murine Th17 differentiation can also be induced in the absence of TGF-β1 signaling, via the combination either of IL-1β, IL-6, and IL-23 or of 42). These TGF-β1-independent Th17 cells can efficiently induce autoimmune tissue inflammation upon adoptive transfer, a trait that led to them being termed "pathogenic" Th17 cells. Additionally, they possess a gene expression profile distinct from that of "nonpathogenic" Th17 cells, which are differentiated with TGF-β1 and IL-6. These observations have led to two competing hypotheses. The first posits that IL-23 cements Th17 lineage commitment such that Th17 cells induced with TGF-β1 and IL-6 are insufficiently committed to the lineage and cannot induce autoimmune tissue inflammation. The second suggests that there are distinct subtypes of Th17 cells whose differentiation is dependent on distinct combinations of cytokines. The latter hypothesis is supported by the finding that pathogenic Th17 cells express higher levels of several Th1 lineage-associated transcripts, such as the transcription factor T-bet and IFN-γ, and have been shown to be derived from IL-17 single producers by fate mapping experiments (43,44). Similarly, an important feature of human Th17 cells, as well as those isolated from inflamed tissues in mouse models of Th17-mediated disease, is that they coproduce IL-17 with other cytokines, leading to distinct functional roles (45)(46)(47). For instance, human Th17 cells that produce both IL-10 and IL-17 preferentially respond to Staphylococcus aureus, while those that produce both IL-17 and IFN-γ recognize Candida albicans, suggesting that distinct pathogens induce distinct subtypes of Th17 cells (40). IL-17/IFN-γ coproducers have been ascribed pathogenic functions in the CNS during EAE; however, it has been difficult to reliably differentiate such cells in vitro. Repeated rounds of in vitro culture in the presence of either Th1-inducing cytokines or IL-23 can induce IL-17/IFN-γ coproducers, albeit at moderate percentages. The transcription factors T-bet, RUNX1, and RUNX3 appear to be important in the acquisition of this phenotype (48,49).Large-scale transcriptional analysis of Th17 differentiation at very high temporal resolution has begun to elucidate the molecular networks that control this process, and is a promising approach to the identification of novel regulatory molecules that control pathogenic Th17 differentiation (50, 51). In fact, Th17 development is controlled induction of this lineage. The combination of TGF-β1 and IL-6 efficiently induces IL-17-producing murine T cells in vitro and highlights the reciprocal relationship between induced Tregs, which are generated by TGF-β1 alone, and Th17 cells (19,20). A series of studies demonstrated that IL-21, a γ c -dependent cytokine, could promote the differentiation of Th17 cells (21-23). In combination with TGF-β, IL-21 induces IL-17 production from naive Th cells and promotes the expression of both RORγt, th...

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“…More recently, gut microbiota has been identified as an important modifier of local as well as systemic inflammatory reactions influencing, except of the intestine, also remote tissues, most notably peripheral blood and AT, especially its visceral compartment, where, via the portal vein, intestinal microbial products are being directly drained into (Burcelin et al 2013). Obesity and T2DM were associated with changes in the amount and composition of gut microbes in experimental animals as well as humans (Carvalho & Saad 2013, Cox & Blaser 2013. Interestingly, different gut microbiota-derived products can exert both pro-and antiinflammatory effects, as e.g.…”

Section: At As Immune Organmentioning

confidence: 99%

The role of adipose tissue immune cells in obesity and low-grade inflammation

Mráz

Haluzı́k

2014

Journal of Endocrinology

437

323

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Adipose tissue (AT) lies at the crossroad of nutrition, metabolism, and immunity; AT inflammation was proposed as a central mechanism connecting obesity with its metabolic and vascular complications. Resident immune cells constitute the second largest AT cellular component after adipocytes and as such play important roles in the maintenance of AT homeostasis. Obesity-induced changes in their number and activity result in the activation of local and later systemic inflammatory response, marking the transition from simple adiposity to diseases such as type 2 diabetes mellitus, arterial hypertension, and ischemic heart disease. This review has focused on the various subsets of immune cells in AT and their role in the development of AT inflammation and obesity-induced insulin resistance.

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Pathways in Microbe-Induced Obesity

Cited by 246 publications

References 99 publications

Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease

Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease

Pouring fuel on the fire: Th17 cells, the environment, and autoimmunity

The role of adipose tissue immune cells in obesity and low-grade inflammation

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