| 1. |
- Caesar, Robert, 1973, et al.
(författare)
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Gut-derived lipopolysaccharide augments adipose macrophage accumulation but is not essential for impaired glucose or insulin tolerance in mice
- 2012
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 61:12, s. 1701-1707
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Tidskriftsartikel (refereegranskat)abstract
- Background Obesity is associated with accumulation of macrophages in white adipose tissue (WAT), which contribute to the development of insulin resistance. Germ-free (GF) mice have reduced adiposity and are protected against diet-induced obesity, Objective To investigate whether the gut microbiota and, specifically, gut-derived lipopolysaccharide (LPS) promote WAT inflammation and contribute to impaired glucose metabolism. Method Macrophage composition and expression of proinflammatory and anti-inflammatory markers were compared in WAT of GF, conventionally raised and Escherichia coli-monocolonised mice. Additionally, glucose and insulin tolerance in these mice was determined. Results The presence of a gut microbiota resulted in impaired glucose metabolism and increased macrophage accumulation and polarisation towards the proinflammatory M1 phenotype in WAT. Monocolonisation of GF mice for 4 weeks with E. coli W3110 or the isogenic strain MLK1067 (which expresses LPS with reduced immunogenicity) resulted in impaired glucose and insulin tolerance and promoted M1 polarisation of CD11b cells in WAT. However, colonisation with E. coli W3110 but not MLK1067 promoted macrophage accumulation and upregulation of proinflammatory and anti-inflammatory gene expression as well as JNK phosphorylation. Conclusion Gut microbiota induced LPS-dependent macrophage accumulation in WAT, whereas impairment of systemic glucose metabolism was not dependent on LPS. These results indicate that macrophage accumulation in WAT does not always correlate with impaired glucose metabolism.
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| 2. |
- Reinhardt, Christopher, et al.
(författare)
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Intestinal microbiota during infancy and its implications for obesity
- 2009
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition. - 1536-4801. ; 48:3, s. 249-56
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Forskningsöversikt (refereegranskat)abstract
- Obesity is a worldwide epidemic, threatening both industrialized and developing countries, and is accompanied by a dramatic increase in obesity-related disorders, including type 2 diabetes mellitus, hypertension, cardiovascular diseases, and nonalcoholic fatty liver disease. Recent studies have shown that the gut microbial community (microbiota) is an environmental factor that regulates obesity by increasing energy harvest from the diet and by regulating peripheral metabolism. However, there are no data on how obesogenic microbiotas are established and whether this process is determined during infancy. The sterile fetus is born into a microbial world and is immediately colonized by numerous species originating from the surrounding ecosystems, especially the maternal vaginal and fecal microflora. This initial microbiota develops into a complex ecosystem in a predictable fashion determined by internal (eg, oxygen depletion) and external (eg, mode of birth, impact of environment, diet, hospitalization, application of antibiotics) factors. We discuss how the gut microbiota regulates obesity and how environmental factors that affect the establishment of the gut microbiota during infancy may contribute to obesity later in life.
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| 3. |
- Muccioli, Giulio G, et al.
(författare)
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The endocannabinoid system links gut microbiota to adipogenesis.
- 2010
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Ingår i: Molecular systems biology. - : EMBO. - 1744-4292. ; 6:392
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is characterised by altered gut microbiota, low-grade inflammation and increased endocannabinoid (eCB) system tone; however, a clear connection between gut microbiota and eCB signalling has yet to be confirmed. Here, we report that gut microbiota modulate the intestinal eCB system tone, which in turn regulates gut permeability and plasma lipopolysaccharide (LPS) levels. The impact of the increased plasma LPS levels and eCB system tone found in obesity on adipose tissue metabolism (e.g. differentiation and lipogenesis) remains unknown. By interfering with the eCB system using CB(1) agonist and antagonist in lean and obese mouse models, we found that the eCB system controls gut permeability and adipogenesis. We also show that LPS acts as a master switch to control adipose tissue metabolism both in vivo and ex vivo by blocking cannabinoid-driven adipogenesis. These data indicate that gut microbiota determine adipose tissue physiology through LPS-eCB system regulatory loops and may have critical functions in adipose tissue plasticity during obesity.
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| 4. |
- Reigstad, Christopher S., et al.
(författare)
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Microbial regulation of SAA3 expression in mouse colon and adipose tissue.
- 2010
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Ingår i: Gut microbes. - : Informa UK Limited. - 1949-0984 .- 1949-0976. ; 1:1, s. 55-57
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Tidskriftsartikel (refereegranskat)abstract
- Recently, we demonstrated that colonic and adipose expression of SAA3 was modulated by the gut microbiota and Toll-like receptor signaling in mice. We observed that SAA3 was expressed by colonic epithelial cells and that its expression was induced in a murine colonocyte cell line following lipopolysaccharide stimulation and nuclear NFκB translocation. In this addendum, we extend this initial study and suggest that SAA3 (1) resembles human SAA1 both in amino acid homology and tissue distribution, (2) appears to have autocrine or paracrine effects rather than endocrine, and (3) binds to bacteria within the gastrointestinal tract. Although speculative, these observations raise the possibility that SAA3 may promote local inflammation in adipose tissue that affects insulin signaling and also function as an antimicrobial agent in the colon.
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| 5. |
- Reigstad, Christopher S., et al.
(författare)
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Regulation of serum amyloid A3 (SAA3) in mouse colonic epithelium and adipose tissue by the intestinal microbiota
- 2009
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota has been proposed as an environmental factor that affects the development of metabolic and inflammatory diseases in mammals. Recent reports indicate that gut bacteria-derived lipopolysaccharide (LPS) can initiate obesity and insulin resistance in mice; however, the molecular interactions responsible for microbial regulation of host metabolism and mediators of inflammation have not been studied in detail. Hepatic serum amyloid A (SAA) proteins are markers and proposed mediators of inflammation that exhibit increased levels in serum of insulin-resistant mice. Adipose tissue-derived SAA3 displays monocyte chemotactic activity and may play a role in metabolic inflammation associated with obesity and insulin resistance. To investigate a potential mechanistic link between the intestinal microbiota and induction of proinflammatory host factors, we performed molecular analyses of germ-free, conventionally raised and genetically modified Myd88-/- mouse models. SAA3 expression was determined to be significantly augmented in adipose (9.9+/-1.9-fold; P<0.001) and colonic tissue (7.0+/-2.3-fold; P<0.05) by the presence of intestinal microbes. In the colon, we provided evidence that SAA3 is partially regulated through the Toll-like receptor (TLR)/MyD88/NF-kappaB signaling axis. We identified epithelial cells and macrophages as cellular sources of SAA3 in the colon and found that colonic epithelial expression of SAA3 may be part of an NF-kappaB-dependent response to LPS from gut bacteria. In vitro experiments showed that LPS treatments of both epithelial cells and macrophages induced SAA3 expression (27.1+/-2.5-fold vs. 1.6+/-0.1-fold, respectively). Our data suggest that LPS, and potentially other products of the indigenous gut microbiota, might elevate cytokine expression in tissues and thus exacerbate chronic low-grade inflammation observed in obesity.
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| 6. |
- Velagapudi, Vidya R., et al.
(författare)
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The gut microbiota modulates host energy and lipid metabolism in mice
- 2009
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 51:5, s. 1101-1112
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota has recently been identified as an environmental factor that may promote metabolic diseases. To investigate the effect of gut microbiota on host energy and lipid metabolism, we compared the serum metabolome and the lipidomes of serum, adipose tissue, and liver of conventionally raised (CONV-R) and germ-free mice. The serum metabolome of CONV-R mice was characterized by increased levels of energy metabolites e.g. pyruvic acid, citric acid, fumaric acid, and malic acid while levels of cholesterol and fatty acids were reduced. We also showed that the microbiota modified a number of lipid species in the serum, adipose tissue and liver, with its greatest effect on triglyceride and phosphatidylcholine species. Triglyceride levels were lower in serum but higher in adipose tissue and liver of CONV-R mice, consistent with increased lipid clearance. Our findings show that the gut microbiota affects both host energy and lipid metabolism, and highlights its role in the development of metabolic diseases.
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