Endotoxaemia leads to major increases in inflammatory adipokine gene expression in white adipose tissue of mice

Leuwer, Martin; Welters, Ingeborg; Marx, Gernot; Rushton, A; Bao, Huihui; Hunter, Leif; Trayhurn, Paul

doi:10.1007/s00424-008-0564-8

Cited by 47 publications

(33 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar to what has been reported for specific TLR agonists (16,24), we observed an inoculum dose-dependent production of IL-6 and MCP-1 (CC chemokine ligand 2), highlighting the potential role of adipocytes in the host immune response to bacterial infections. At the same time, infection with S. aureus profoundly altered the secretion of adipokines by differentiated adipocytes.…”

Section: Discussionsupporting

confidence: 87%

Intracellular Survival of Staphylococcus aureus in Adipocyte-Like Differentiated 3T3-L1 Cells Is Glucose Dependent and Alters Cytokine, Chemokine, and Adipokine Secretion

et al. 2011

View full text Add to dashboard Cite

Although obesity and type 2 diabetes mellitus are associated with Gram-positive infections and a worse clinical outcome, it is unknown whether adipocytes can be infected by Gram-positive bacteria. Adipocyte-like differentiated 3T3-L1 cells and Staphylococcus aureus were used for infection experiments under normoglycemic (100 mg/dl) and hyperglycemic (450 mg/dl) conditions in the presence/absence of insulin (1 μm). Intracellular presence and survival of S. aureus was investigated quantitatively. Supernatant cytokines, chemokines, and adipokines were measured by ELISA. Lipid metabolism and cellular morphology of infected adipocytes were investigated by different techniques. The present study provides the proof of principle that adipocyte-like cells can be infected by S. aureus dose dependently for up to 5 d. Importantly, low bacterial inocula did not affect cell viability. Intracellular survival of S. aureus was glucose dependent but not insulin dependent, and insulin receptor expression and insulin receptor signaling were not altered. Infection increased macrophage chemoattractant protein-1, visfatin, and IL-6 secretion, whereas resistin and adiponectin were decreased. Infected adipocytes had higher intracellular triacylglycerol concentrations and larger lipid droplets because of a decreased lipolysis. Taken together, infection of adipocytes by S. aureus is glucose dependent, inhibits cellular lipolysis, and affects the secretion of immunomodulating adipokines differentially. Because cell viability is not affected during infection, adipose tissue might function as a host for chronic infection by bacteria-causing metabolic, proinflammatory, and prodiabetic disturbances.

show abstract

Section: Discussionsupporting

confidence: 87%

Intracellular Survival of Staphylococcus aureus in Adipocyte-Like Differentiated 3T3-L1 Cells Is Glucose Dependent and Alters Cytokine, Chemokine, and Adipokine Secretion

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Previously, it was reported that a large dose of LPS (24 mg/kg) that resulted in a high prevalence of death (39%) in mice increased inflammatory gene expression (i.e. TNFa, IL-6, MCP-1) in WAT from surviving mice, but, notably, F4/80 and CD11b macrophage marker transcript levels did not increase 24 h after LPS injection (67). In the acute, high-dose LPS model, we observed strong activation of WAT transcript levels for a suite of proinflammatory markers, but, interestingly, some macrophage-associated markers such as CD68 and the CD11 family members were reduced, unlike in the 5-d, low-dose LPS studies.…”

Section: Discussionmentioning

confidence: 98%

Inflammatory Phenotyping Identifies CD11d as a Gene Markedly Induced in White Adipose Tissue in Obese Rodents and Women

Thomas

Dunn

Oort

et al. 2011

The Journal of Nutrition

View full text Add to dashboard Cite

In severe obesity, white adipose tissue (WAT) inflammation and macrophage infiltration are thought to contribute to WAT and whole-body insulin resistance. Specific players involved in triggering and maintaining inflammation (i.e. those regulating adipokine release and WAT macrophage recruitment, retention, or function) remain to be fully elaborated, and the degree to which moderate obesity promotes WAT inflammation remains to be clarified further. Therefore, we characterized adiposity and metabolic phenotypes in adult male C57BL/6J mice fed differing levels of dietary fat (10, 45, and 60% of energy) for 12 wk, concurrent with determinations of WAT inflammation markers and mRNA expression of leukocyte-derived integrins (CD11b, CD11c, CD11d) involved in macrophage extravasation and tissue macrophage homing/retention. As expected, a lard-based, very high-fat diet (60% energy) significantly increased adiposity and glucose intolerance compared with 10% fat-fed controls, coincident with higher retroperitoneal (RP) WAT transcript levels for proinflammatory factors and macrophage markers, including TNFα and CD68 mRNA, which were ~3- and ~15-fold of control levels, respectively (P < 0.001). Mice fed the 45% fat diet had more moderate obesity, less glucose intolerance, and lower WAT macrophage/inflammatory marker mRNA abundances compared with 60% fat-fed mice; TNFα and CD68 mRNA levels were ~2- and ~5-fold of control levels (P < 0.01). Relative WAT expression of CD11d was massively induced by obesity to an extent greater than any other inflammatory marker (to >300-fold of controls in the 45 and 60% fat groups) (P < 0.0001) and this induction was WAT specific. Because we found that CD11d expression also increased in RP-WAT of Zucker obese rats and in the subcutaneous WAT of obese adult women, this appears to be a common feature of obesity. Observed correlations of WAT macrophage transcript marker abundances with body weight in lean to modestly obese mice raises an interesting possibility that the activities of at least some WAT macrophages are closely linked to the normal adipose remodeling that is a requisite for changes in WAT energy storage capacity.

show abstract

“…Although acute inflammation in vitro has well-described negative effects on adiponectin biosynthesis in cultured adipocytes, 14 the effects of acute inflammation in vivo are unclear; in mice, lipopolysaccharide injection lowers ADIPOQ gene expression from white AT, 30 but in patients with diabetes mellitus, short-term infusion of IL-6 increases ADIPOQ gene expression in subcutaneous AT. 31 We induced systemic low-grade inflammation in healthy individuals by using S. typhi vaccine, 23 and we observed that this type of inducible inflammation decreased circulating adiponectin levels within 24 hours compared with placebo, having no effects on circulating BNP.…”

Section: Discussionmentioning

confidence: 99%

Reciprocal Effects of Systemic Inflammation and Brain Natriuretic Peptide on Adiponectin Biosynthesis in Adipose Tissue of Patients With Ischemic Heart Disease

Antonopoulos

Margaritis

Coutinho

et al. 2014

ATVB

100

View full text Add to dashboard Cite

Objective-To explore the role of systemic inflammation in the regulation of adiponectin levels in patients with ischemic heart disease. Approach and Results-In a cross-sectional study of 575 subjects, serum adiponectin was compared between healthy subjects, patients with coronary artery disease with no/mild/severe heart failure (HF), and patients with nonischemic HF. Adiponectin expression and release from femoral, subcutaneous and thoracic adipose tissue was determined in 258 additional patients with coronary artery bypass grafting. Responsiveness of the various human adipose tissue depots to interleukin-6, tumor necrosis factor-α, and brain natriuretic peptide (BNP) was examined by using ex vivo models of human fat. The effects of inducible low-grade inflammation were tested by using the model of Salmonella typhi vaccine-induced inflammation in healthy individuals. In the cross-sectional study, HF strikingly increased adiponectin levels. Plasma BNP was the strongest predictor of circulating adiponectin and its release from all adipose tissue depots in patients with coronary artery bypass grafting, even in the absence of HF. Femoral AT was the depot with the least macrophages infiltration and the largest adipocyte cell size and the only responsive to systemic and ex vivo proinflammatory stimulation (effect reversible by BNP). Low-grade inflammation reduced circulating adiponectin levels, while circulating BNP remained unchanged. Conclusions-This study demonstrates the regional variability in the responsiveness of human adipose tissue to systemic inflammation and suggests that BNP (not systemic inflammation) is the main driver of circulating adiponectin in patients with advanced atherosclerosis even in the absence of HF. Any interpretation of circulating adiponectin as a biomarker should take into account the underlying disease state, background inflammation, and BNP levels.

show abstract

Endotoxaemia leads to major increases in inflammatory adipokine gene expression in white adipose tissue of mice

Cited by 47 publications

References 56 publications

Intracellular Survival of Staphylococcus aureus in Adipocyte-Like Differentiated 3T3-L1 Cells Is Glucose Dependent and Alters Cytokine, Chemokine, and Adipokine Secretion

Intracellular Survival of Staphylococcus aureus in Adipocyte-Like Differentiated 3T3-L1 Cells Is Glucose Dependent and Alters Cytokine, Chemokine, and Adipokine Secretion

Inflammatory Phenotyping Identifies CD11d as a Gene Markedly Induced in White Adipose Tissue in Obese Rodents and Women

Reciprocal Effects of Systemic Inflammation and Brain Natriuretic Peptide on Adiponectin Biosynthesis in Adipose Tissue of Patients With Ischemic Heart Disease

Contact Info

Product

Resources

About