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- Benrick, Anna, 1979, et al.
(författare)
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Elevated interlukin-6 levels as a consequence, not the cause of obesity and insulin resistance
- 2013
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Ingår i: Interleukin-6: Genetics, Clinical Applications and Role in Disease. - : Nova Science Publishers, Inc.. - 9781624175923 ; , s. 197-210
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Bokkapitel (refereegranskat)abstract
- Several population-based studies have reported that serum interleukin-6 (IL-6) levels are positively correlated with obesity and insulin resistance. This has lead to the hypothesis of a causal relationship between elevated IL-6 levels and insulin resistance. This notion is further strengthened by the observation that obesity is associated with a chronic low-grade inflammation in adipose tissue, which is postulated to be causal in the development of insulin resistance and type-2 diabetes. A recent study of weight gain demonstrates however that insulin resistance develops even in the absence of a significant signs of adipose inflammation. This suggests that inflammation in adipose tissue occurs subsequent to peripheral insulin resistance in humans. More and more data also supports the hypothesis that increased adiposity in itself, independent of the increased IL-6 levels, is a predictor of diabetes risk. IL-6 levels tend to also increase with age and since the incidence of insulin resistance and type-2 diabetes also increases with age, this could explain some of the observed correlations. Taken together, the above studies provide an association of metabolic disorder with IL-6, but not causation. An emerging concept is that IL-6 appears to have different effects on different tissues, and the effects depend on whether the IL-6 levels are acutely or chronically elevated. Given the opposing views of the impact of IL-6 on glucose homeostasis, many investigations have aimed at clarifying the effects of IL-6 on insulin action. A recent study shows that IL-6, either released from skeletal muscle or adipose tissue, induces GLP-1 release, leading to insulin secretion, improved beta-cell function and glycemic control. Still, the causal relationships between IL-6, obesity and type-2 diabetes remain a matter of debate. This review summarizes the current data on IL-6, supporting an association, but not a causative relationship, between IL-6 and metabolic disturbances. © 2013 Nova Science Publishers, Inc. All rights reserved.
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| 2. |
- Benrick, Anna, 1979, et al.
(författare)
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Interleukin-6 mediates exercise-induced increase in insulin sensitivity in mice.
- 2012
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Ingår i: Experimental physiology. - : Wiley. - 1469-445X .- 0958-0670. ; 97:11 SI, s. 1224-1235
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-6 (IL-6) is released from working skeletal muscle during exercise. We investigated the acute and the long-term beneficial effects of IL-6 on exercise-induced glucose uptake in skeletal muscle and insulin sensitivity. The acute effect on exercise-induced glucose uptake was measured in IL-6 deficient (-/-) mice and wild type controls using a tracer technique. There was no difference in serum disappearance of 3H-2-deoxyglucose after a bolus dose of exercise between IL-6 -/- and wild type mice (13565 ± 426 vs. 14343 ± 1309 dpm*min/ml, p=0.5). The glucose uptake rate in the EDL muscle was however lower in IL-6 -/- compared to wildtype mice (398 ± 44 vs. 657 ± 41 nmol/g/min, p<0.01). In the long-term study, we monitored insulin sensitivity, serum retinol-binding protein-4 (RBP-4) levels, running activity, food intake, body weight and body composition in IL-6 -/- and wild type mice on a high-fat diet (HFD), with or without access to running wheels. In sedentary IL-6 -/- and wild type mice, HFD decreased insulin sensitivity (glucose AUC increased about 20% during an insulin tolerance test (ITT), p<0.05 for both genotypes vs. baseline) and led to a 30% increase in serum RBP-4 levels (p <0.01 for both genotypes vs. baseline). Wild type runners were protected against these effects of HFD and maintained their baseline insulin sensitivity and serum RBP-4 levels. In contrast, IL-6 -/- mice did not, to the same extent as wild types, benefit from running. IL-6 -/- runners had a similar decrease in insulin sensitivity as their sedentary littermates (glucose AUC during an ITT in runners vs. sedentary IL-6-/- HFD mice: 312 ± 14 vs. 340 ± 22 mmol*min/L, p=0.4) and displayed a 14% increase in serum RBP-4 as compared to baseline levels (p<0.01). Our results indicate that endogenous IL-6 contributes to the exercise-induced increase in insulin sensitivity, but only plays a minor role for glucose uptake into skeletal muscle during exercise.
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| 3. |
- Lager, Susanne, 1978, et al.
(författare)
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Perinatal lack of maternal IL-6 promotes increased adiposity during adulthood in mice.
- 2011
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 152:4, s. 1336-46
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Tidskriftsartikel (refereegranskat)abstract
- The perinatal environment appears important in establishing metabolic phenotypes in adulthood. Mice deficient in IL-6 (IL-6(-/-)) tend to develop mature-onset obesity, but it is unknown whether perinatal exposure to IL-6 produced by the dam influences the metabolism of adult offspring. To address this issue, we monitored IL-6(-/-) offspring of IL-6(-/-) or IL-6(+/-) dams, as well as wild-type (WT) mice. At adult age, IL-6(-/-) mice weighed significantly more and had more body fat than WT mice, regardless of maternal genotype, and had lower insulin sensitivity. This phenotype was more pronounced in IL-6(-/-) offspring of IL-6(-/-) dams, because they gained weight significantly faster than IL-6(-/-) offspring of IL-6(+/-) dams and had more body fat and higher serum leptin levels at an earlier age. The leptin content was 2-fold higher in milk from IL-6(-/-) than WT dams. However, cross-fostering IL-6(-/-) mice with WT dams did not alter body weight, body composition, or adipocyte size at adult age compared with IL-6(-/-) mice fostered by IL-6(-/-) dams. Conversely, WT mice fostered by IL-6(-/-) dams weighed significantly more than those fostered by WT dams and had more body fat, larger adipocytes, and altered hypothalamic gene expression. We conclude that body fat of adult mice can be increased by perinatal exposure to factors affected by lack of maternal IL-6.
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| 4. |
- Wernstedt Asterholm, Ingrid, 1978, et al.
(författare)
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Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling.
- 2014
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Ingår i: Cell metabolism. - : Elsevier BV. - 1932-7420 .- 1550-4131. ; 20:1, s. 103-18
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Tidskriftsartikel (refereegranskat)abstract
- Chronic inflammation constitutes an important link between obesity and its pathophysiological sequelae. In contrast to the belief that inflammatory signals exert a fundamentally negative impact on metabolism, we show that proinflammatory signaling in the adipocyte is in fact required for proper adipose tissue remodeling and expansion. Three mouse models with an adipose tissue-specific reduction in proinflammatory potential were generated that display a reduced capacity for adipogenesis in vivo, while the differentiation potential is unaltered in vitro. Upon high-fat-diet exposure, the expansion of visceral adipose tissue is prominently affected. This is associated with decreased intestinal barrier function, increased hepatic steatosis, and metabolic dysfunction. An impaired local proinflammatory response in the adipocyte leads to increased ectopic lipid accumulation, glucose intolerance, and systemic inflammation. Adipose tissue inflammation is therefore an adaptive response that enables safe storage of excess nutrients and contributes to a visceral depot barrier that effectively filters gut-derived endotoxin.
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| 5. |
- Wernstedt Asterholm, Ingrid, 1978, et al.
(författare)
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Elevated resistin levels induce central leptin resistance and increased atherosclerotic progression in mice.
- 2014
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 57:1, s. 1209-1218
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Tidskriftsartikel (refereegranskat)abstract
- Resistin was originally identified as an adipocyte-derived factor upregulated during obesity and as a contributor to obesity-associated insulin resistance. Clinically, resistin has also been implicated in cardiovascular disease in a number of different patient populations. Our aim was to simultaneously address these phenomena.
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