The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase.

Kern, Philip A.; Saghizadeh, Mehrnoosh; Ong, John M.; Bosch, Ricardo J.; Deem, Richard L.; Simsolo, Rosa B.

doi:10.1172/jci117899

Cited by 1,172 publications

(800 citation statements)

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“…The recent finding that adipose tissue is an active endocrine organ and produces several inflammatory mediators provided a unifying mechanism for the linkage between the incidences of chronic diseases. The most abundant protein in adipose tissue is adiponectin, which stimulates immune cells to produce anti-inflammatory cytokines and may explain disturbed immune function in severely obese individuals (4,5) ; adipose tissue has also been shown to overproduce TNFa and IL-6 in obesity (6)(7)(8)(9) . Obesity is associated with a steady infiltration of macrophages into adipose tissue such that in grossly obese individuals, macrophages constitute up to 40% of the cellular population of the tissue (10) .…”

Section: Influence Of Adipose Tissue Mass On Inflammatory Stressmentioning

confidence: 99%

The true cost of in-patient obesity: impact of obesity on inflammatory stress and morbidity

Grimble

2010

Proc. Nutr. Soc.

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The objective of the present review is to provide an overview of the metabolic effects of pro-inflammatory cytokine production during infection and injury; to highlight the disadvantages of pro-inflammatory cytokine production and inflammatory stress on morbidity and mortality of patients; to identify the influence of genetics and adiposity on inflammatory stress in patients and to indicate how nutrients may modulate the inflammatory response in patients. Recent research has shown clearly that adipose tissue actively secretes a wide range of pro- and anti-inflammatory cytokines. Paradoxically, although inflammation is an essential part of the response of the body to infection, surgery and trauma, it can adversely affect patient outcome. The metabolic effects of inflammation are mediated by pro-inflammatory cytokines. Metabolic effects include insulin insensitivity, hyperlipidaemia, muscle protein loss and oxidant stress. These effects, as well as being present during infective disease, are also present in diseases with a covert inflammatory basis. These latter diseases include obesity and type 2 diabetes mellitus. Inflammatory stress also increases during aging. The level of cytokine production, within individuals, is influenced by single nucleotide polymorphisms (SNP) in cytokine genes. The combination of SNP controls the relative level of inflammatory stress in both overt and covert inflammatory diseases. The impact of cytokine genotype on the intensity of inflammatory stress derived from an obese state is unknown. While studies remain to be done in the latter context, evidence shows that these genomic characteristics influence morbidity and mortality in infectious disease and diseases with an underlying inflammatory basis and thereby influence the cost of in-patient obesity. Antioxidants andn-3 PUFA alter the intensity of the inflammatory process. Recent studies show that genotypic factors influence the effectiveness of immunonutrients. A better understanding of this aspect of nutrient–gene interactions and of the genomic factors that influence the intensity of inflammation during disease will help in the more effective targeting of nutritional therapy.

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Section: Influence Of Adipose Tissue Mass On Inflammatory Stressmentioning

confidence: 99%

The true cost of in-patient obesity: impact of obesity on inflammatory stress and morbidity

Grimble

2010

Proc. Nutr. Soc.

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“…Adipose tissue is currently held to be the greatest source of circulating TNF-α, as well as of other endocrine mediators, collectively referred to as 'adipokines'. Likewise, plasma TNF-α levels have been shown to correlate directly with body fat mass [36]. TNF-α modulates insulin action by promoting serine-phosphorylation of IRS-1, which leads to the downregulation of IRS-1 signalling (Figure 3) [37,38], an effect similar to that of FFA.…”

Section: Non-alcoholic Fatty Liver Diseasementioning

confidence: 97%

Diabetes in chronic liver disease: from old concepts to new evidence

Picardi

D’Avola

Gentilucci

et al. 2006

Diabetes Metab. Res. Rev.

102

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SummaryThe liver is one of the principal organs involved in glucose metabolism together with skeletal muscle and adipose tissue. A link between diabetes and chronic liver disease (CLD) was first observed in the early half of the last century, but to date several questions remain unsolved. Altered glucose tolerance has been well described in alcoholic CLD, non-alcoholic fatty liver disease, chronic hepatitis C and portal hypertension. Moreover, insulin resistance is assuming an ever-growing importance in CLD; chronic hepatitis C has recently been proposed as a metabolic disease and insulin sensitivity as a predictive factor for liver fibrosis.CLD is also complicated by acquired growth hormone (GH) resistance, characterized by low concentrations of insulin-like growth factor-1 (IGF-1) with respect to normal or elevated GH levels. GH resistance in CLD is determined by several factors, including malnutrition, impaired liver function and reduced expression of hepatic GH receptors. We recently described the possible role of tumour necrosis factor-alpha (TNF-α) in blunting the hepatic response to GH in patients with chronic hepatitis C. The role of GH in impaired glucose metabolism is well known, and recent evidence suggests a receptor and/or post-receptor modulation of insulin signalling. Moreover, as in other chronic inflammatory conditions, pro-inflammatory cytokines may directly modulate the signal cascade that follows insulin binding to its receptor in the course of CLD.In this review, the proposed links between impaired glucose tolerance and CLD are analysed, special emphasis being focussed on the most recent findings concerning the interplay of chronic inflammation, GH resistance and insulin resistance.

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“…It affects insulin resistance via two major mechanisms, inhibition of insulin receptor signalling [3] and down-regulation of the GLUT4 glucose transporter [4]. This was thought to occur via the actions of adipose-derived TNF-α, through autocrine mechanisms in adipose tissue and paracrine effects on skeletal muscle [5]. Indeed, TNF-α levels are higher in the adipose tissue of obese and insulin-resistant rodents and humans than in healthy animals or individuals [1,2,5,6].…”

Section: Introductionmentioning

confidence: 99%

“…This was thought to occur via the actions of adipose-derived TNF-α, through autocrine mechanisms in adipose tissue and paracrine effects on skeletal muscle [5]. Indeed, TNF-α levels are higher in the adipose tissue of obese and insulin-resistant rodents and humans than in healthy animals or individuals [1,2,5,6]. More recently it has been shown that TNF-α is also expressed in skeletal muscle and that levels are four-fold higher in insulin-resistant, obese humans than in healthy humans [7].…”

Section: Introductionmentioning

confidence: 99%

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Diet but not aerobic exercise training reduces skeletal muscle TNF-a in overweight humans

et al. 2004

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Aims/hypothesis. Our aim was to test the hypothesis that TNF-α protein levels in skeletal muscle are important in mediating the improvements in glucose homeostasis that are associated with diet and exercise regimens intended to reduce cardiovascular risk. Methods. We recruited 20 people with a body mass index of 32.1±1.2 kg/m 2 (mean ± SEM) and one other component of the metabolic syndrome. The average age was 51.2±8.1 years (mean ± SD). Of the 20 subjects, 6 were men and 14 were women. All subjects completed an 8-week control period, followed by randomisation to 8 weeks of moderate cycling exercise (30 min, three times per week) or to a diet with the following characteristics: low in saturated fat, high in fibre, low glycaemic index, rich in complex carbohydrates.Results. Diet induced a small reduction in body mass index (3.0±0.7%, p<0.05), although weight loss was not intended. Exercise training increased maximum oxygen consumption by 12±6% (p<0.05). Both interventions reduced fasting plasma insulin levels by about 20%. Diet reduced skeletal muscle TNF-α protein by 54±10% (p<0.05), an effect that was independent (p=0.94 in covariate analysis) of the small concurrent weight loss (−2.8±0.7 kg). Levels of GLUT4 protein were unchanged in the diet group. In contrast, exercise training did not significantly change TNF-α protein expression, but GLUT4 protein expression increased by 105±37% (p<0.05). Conclusions/interpretation. These data indicate that the metabolic benefits of a diet aimed at cardiovascular risk reduction are associated with a decrease in skeletal muscle TNF-α protein.

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The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase.

Cited by 1,172 publications

References 59 publications

The true cost of in-patient obesity: impact of obesity on inflammatory stress and morbidity

The true cost of in-patient obesity: impact of obesity on inflammatory stress and morbidity

Diabetes in chronic liver disease: from old concepts to new evidence

Diet but not aerobic exercise training reduces skeletal muscle TNF-a in overweight humans

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