Associations between insulin resistance and TNF-α in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes

Plomgaard, Peter; Nielsen, Annemette; Fischer, Christian P.; Mortensen, Ole Hartvig; Broholm, Christa; Penkowa, Milena; Krogh-Madsen, Rikke; Erikstrup, Christian; Lindegaard, Birgitte; Petersen, Anders Højgård; Taudorf, Sarah; Pedersen, Bente Klarlund

doi:10.1007/s00125-007-0834-6

Cited by 128 publications

(87 citation statements)

References 42 publications

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“…Participants were carefully screened, and exclusion criteria were treatment with insulin, recent or ongoing infection, history of malignant disease, or treatment with anti-inflammatory drugs. Subjects and protocol have been previously described (21,22). Participants (n ϭ 199) were given both oral and written information about the experimental procedures before giving their written informed consent.…”

Section: Methodsmentioning

confidence: 99%

Plasma YKL-40

et al. 2008

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OBJECTIVE-YKL-40 is produced by macrophages, and plasma YKL-40 is elevated in patients with diseases characterized by inflammation. In the present study, YKL-40 was examined in relation to obesity, inflammation, and type 2 diabetes.RESEARCH DESIGN AND METHODS-Plasma YKL-40 and adipose tissue YKL-40 mRNA levels were investigated in 199 subjects who were divided into four groups depending on the presence or absence of type 2 diabetes and obesity. In addition, plasma YKL-40 was examined in healthy subjects during a hyperglycemic clamp, in which the plasma glucose level was kept at 15 mmol/l for 3 h, and during a hyperinsulinemiceuglycemic clamp. -40 (76.7 vs. 45.1 ng/ml, P ϭ 0.0001) but not higher expression in adipose tissue YKL-40 mRNA (1.20 vs. 0.98, P ϭ 0.2) compared with subjects with a normal glucose tolerance. Within the groups with normal glucose tolerance and type 2 diabetes, obesity subgroups showed no difference with respect to either plasma YKL-40 or adipose tissue YKL-40 mRNA levels. Multivariate regression analysis showed that plasma YKL-40 was associated with fasting plasma glucose (␤ ϭ 0.5, P ϭ 0.0014) and plasma interleukin (IL)-6 (␤ ϭ 0.2, P ϭ 0.0303). Plasma YKL-40 was not related to parameters of obesity. There were no changes in plasma YKL-40 in healthy subjects during either hyperglycemic or hyperinsulinemic-euglycemic clamps. RESULTS-Patientswith type 2 diabetes had higher plasma YKLCONCLUSIONS-Plasma YKL-40 was identified as an obesityindependent marker of type 2 diabetes related to fasting plasma glucose and plasma IL-6 levels. Diabetes 57:3078-3082, 2008

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Section: Methodsmentioning

confidence: 99%

Plasma YKL-40

et al. 2008

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“…Mounting evidence suggests that TNF-␣ plays a direct role in the metabolic syndrome (284). Patients with type 2 diabetes demonstrate a high protein expression of TNF-␣ in skeletal muscle and increased TNF-␣ levels in plasma (286,363).…”

Section: Anti-inflammatory Effects Of Interleukin-6mentioning

confidence: 99%

Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6

Pedersen¹,

Febbraio²

2008

Physiological Reviews

1,723

1,576

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Skeletal muscle has recently been identified as an endocrine organ. It has, therefore, been suggested that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert paracrine, autocrine, or endocrine effects should be classified as “myokines.” Recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. However, the first identified and most studied myokine is the gp130 receptor cytokine interleukin-6 (IL-6). IL-6 was discovered as a myokine because of the observation that it increases up to 100-fold in the circulation during physical exercise. Identification of IL-6 production by skeletal muscle during physical activity generated renewed interest in the metabolic role of IL-6 because it created a paradox. On one hand, IL-6 is markedly produced and released in the postexercise period when insulin action is enhanced but, on the other hand, IL-6 has been associated with obesity and reduced insulin action. This review focuses on the myokine IL-6, its regulation by exercise, its signaling pathways in skeletal muscle, and its role in metabolism in both health and disease.

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“…103 TNF-a is a strong inducer of lipolysis 104 and data from rodents and humans support a role in the development of insulin resistance. [105][106][107] The latter, however, has been challenged by others 108 and although TNF-a levels are increased in obesity, 109,110 there is little direct release from abdominal subcutaneous adipose tissue in vivo. 111 Interestingly, in a similar set of studies it was found that abdominal subcutaneous adipose tissue releases the soluble TNF receptor type 1 and that its levels correlate with BMI.…”

Section: Inflammatory Cytokinesmentioning

confidence: 99%

Gluteofemoral body fat as a determinant of metabolic health

2010

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Body fat distribution is an important metabolic and cardiovascular risk factor, because the proportion of abdominal to gluteofemoral body fat correlates with obesity-associated diseases and mortality. Here, we review the evidence and possible mechanisms that support a specific protective role of gluteofemoral body fat. Population studies show that an increased gluteofemoral fat mass is independently associated with a protective lipid and glucose profile, as well as a decrease in cardiovascular and metabolic risk. Studies of adipose tissue physiology in vitro and in vivo confirm distinct properties of the gluteofemoral fat depot with regards to lipolysis and fatty acid uptake: in day-to-day metabolism it appears to be more passive than the abdominal depot and it exerts its protective properties by long-term fatty acid storage. Further, a beneficial adipokine profile is associated with gluteofemoral fat. Leptin and adiponectin levels are positively associated with gluteofemoral fat while the level of inflammatory cytokines is negatively associated. Finally, loss of gluteofemoral fat, as observed in Cushing's syndrome and lipodystrophy is associated with an increased metabolic and cardiovascular risk. This underlines gluteofemoral fat's role as a determinant of health by the long-term entrapment of excess fatty acids, thus protecting from the adverse effects associated with ectopic fat deposition.

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Associations between insulin resistance and TNF-α in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes

Cited by 128 publications

References 42 publications

Plasma YKL-40

Plasma YKL-40

Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6

Gluteofemoral body fat as a determinant of metabolic health

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