The equivocal metabolic response to endotoxaemia in type 2 diabetic and obese ZDF rats

Senon, Géraldine; Blanc, M; Paillard, A.; Cynober, Luc; Darquy, Sylviane

doi:10.1007/s00125-006-0233-4

Cited by 15 publications

(5 citation statements)

References 45 publications

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“…Non-adherent cells were removed after incubation for 2 h, and macrophages were cultured in arginine-free Dulbecco's modified Eagle's medium (Eurobio) for 6 h in the presence of 0·1, 0·5, 1 or 2 m m -citrulline. The lowest concentration corresponded to the physiological plasma concentration of citrulline in Zucker diabetic fatty rats (about 100 μmol/l for diabetic obese and lean rats) ( 3 ) , and the other concentrations were in the range of peak plasma concentrations observed previously after in vivo citrulline administration in rats ( 15 , 16 ) . At the end of the incubation period, the culture media were collected and stored at − 80°C until analysis ( 1 ) .…”

Section: Methodsmentioning

confidence: 68%

“…Various alterations in immune defence have been observed in animal models of insulin resistance, notably including an impairment in cytokine and NO production by peritoneal macrophages ( 1 , 2 ) . This may be attributed to the progressive decrease in the plasma concentration of arginine, the NO precursor, that develops with the metabolic syndrome and T2D ( 3 ) .…”

mentioning

confidence: 99%

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In vitroanti-inflammatory effects of citrulline on peritoneal macrophages in Zucker diabetic fatty rats

et al. 2014

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In type 2 diabetes (T2D) macrophage dysfunction increases susceptibility to infection and mortality. This may result from the associated decreased plasma concentration of arginine, an amino acid that plays an important role in immunity. In vitro, increasing arginine availability leads to an improvement in macrophage function; however, arginine supplementation in diabetic obese patients may be detrimental. The aim of the present study was to assess in vitro whether citrulline, an arginine precursor, could replace arginine in the regulation of macrophage function under a condition of diabetes and obesity. Peritoneal macrophages from diabetic obese or lean rats were incubated for 6 h in an arginine-free medium, in the presence of increasing citrulline concentrations (0·1, 0·5, 1 or 2 mmol/l). Cytokine and NO production was determined. Peritoneal macrophages from either lean or diabetic obese rats produced NO, and at higher levels in the cells from lean rats. In diabetic obese rats, TNF-a production decreased with increasing citrulline concentrations, but was higher than that in the cells from lean rats. In contrast, IL-6 production increased with increasing citrulline concentrations. The present experiment shows that citrulline is effectively used for NO production and regulates cytokine production in macrophages from diabetic obese rats. This effect warrants in vivo evaluation in T2D-related inflammation.

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Section: Methodsmentioning

confidence: 68%

mentioning

confidence: 99%

In vitroanti-inflammatory effects of citrulline on peritoneal macrophages in Zucker diabetic fatty rats

et al. 2014

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“…For example, E. coli ‐derived LPS‐treated (i.p. injection) diabetic Zucker rats did not show impaired metabolic responses and were less sensitive to stress compared with lean littermates [135]. There also appears to be an adaptation over time based on exposure.…”

Section: Impact Of Obesity: a Larger Lps Reservoir?mentioning

confidence: 99%

Lipopolysaccharide and the gut microbiota: considering structural variation

et al. 2022

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Systemic inflammation is associated with chronic disease and is purported to be a main pathogenic mechanism underlying metabolic conditions. Microbes harbored in the host gastrointestinal tract release signaling byproducts from their cell wall, such as lipopolysaccharides (LPS), which can act locally and, after crossing the gut barrier and entering circulation, also systemically. Defined as metabolic endotoxemia, elevated concentrations of LPS in circulation are associated with metabolic conditions and chronic disease. As such, measurement of LPS is highly prevalent in animal and human research investigating these states. Indeed, LPS can be a potent stimulant of host immunity, but this response depends on the microbial species’ origin, a parameter often overlooked in both preclinical and clinical investigations. Indeed, the lipid A portion of LPS is mutable and comprises the main virulence and endotoxic component, thus contributing to the structural and functional diversity among LPSs from microbial species. In this review, we discuss how such structural differences in LPS can induce differential immunological responses in the host.

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“…However, not all obese people (or animals) become sick or develop complications. For example, fa/fa Zucker rats do not show impaired metabolic responses to LPS (8), and diet‐induced obesity has also been associated with attenuated (not exacerbated) immune responses to Porphyromonas gingivalis infection (9). It is therefore likely that, in the obese, additional factors contribute to changes in the ability to respond to an immune challenge.…”

mentioning

confidence: 99%

Postnatal Overfeeding Leads to Obesity and Exacerbated Febrile Responses to Lipopolysaccharide Throughout Life

Clarke

Stefanidis

Spencer

2012

J Neuroendocrinology

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The perinatal environment can be crucial for programming long-term physiology, including the mechanisms regulating body weight, and postnatal overfeeding can lead to obesity throughout life. Inflammation-related complications are of particular concern in the obese. However, little is known about how postnatal overfeeding contributes to changes in the ability to respond to inflammation. In the present study, we investigate changes in the febrile and neurochemical response to immune challenge with lipopolysaccharide (LPS), in juvenile and adult, male and female Wistar rats made obese by overfeeding during the postnatal period. We demonstrate that febrile responses to LPS are exacerbated in these rats, with peak core temperatures being up to 0.5 °C higher compared to those in controls, and this is associated with an enhanced pro-inflammatory cytokine profile and enhanced hypothalamic-pituitary-adrenal (HPA) axis activation. Plasma pro-inflammatory cytokines concentrations were approximately three-fold greater in neonatally overfed rats after LPS and there were approximately twice as many neurones activated in the paraventricular nucleus of the hypothalamus as in controls, with a prolonged corticosterone response. We also observed elevated expression of toll-like receptors (TLR) 2 and 4 in adipose tissue and greater inhibitory factor κB phosphorylation in these obese animals. Despite similar changes in expression of adipose TLR3, there was no corresponding alteration in the response to a viral mimetic that acts at this receptor. We suggest that an elevated febrile response to LPS therefore occurs in cases of obesity and this is associated with altered HPA axis function and enhanced TLR2/4 expression in adipose tissue and an up-regulated downstream pro-inflammatory cascade.

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The equivocal metabolic response to endotoxaemia in type 2 diabetic and obese ZDF rats

Cited by 15 publications

References 45 publications

In vitroanti-inflammatory effects of citrulline on peritoneal macrophages in Zucker diabetic fatty rats

In vitroanti-inflammatory effects of citrulline on peritoneal macrophages in Zucker diabetic fatty rats

Lipopolysaccharide and the gut microbiota: considering structural variation

Postnatal Overfeeding Leads to Obesity and Exacerbated Febrile Responses to Lipopolysaccharide Throughout Life

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