| 1. |
- Jansson, John-Olov, 1954, et al.
(författare)
-
On the site and mechanism of action of the anti-obesity effects of interleukin-6.
- 2003
-
Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - 1096-6374. ; 13 Suppl A
-
Tidskriftsartikel (refereegranskat)abstract
- We conducted an experimental study examining the site and mechanism of action of the anti-obesity effect of interleukin-6 (IL-6) in mice and rats. We used dual energy X-ray absorptiometry (DEXA) and computerized tomography to investigate the body composition of mice with knockout of the IL-6 gene and wild-type control mice. Rats were treated with IL-6 or vehicle through intracerebroventricular (ICV) cannulae. Energy expenditure was measured as oxygen consumption by indirect calorimetry in metabolic chambers. Results showed that the mice lacking IL-6 increased in body weight compared with wild-type mice from 6 months of age onward, although there was no marked difference in food intake between the pre-obese IL-6 knockout mice and the wild-type mice. IL-6 given as a single ICV injection to rats stimulated oxygen consumption; whereas, the same doses were ineffective when given peripherally. Chronic ICV IL-6 treatment decreased body weight and fat mass in rodents. Administration of IL-6 may decrease fat mass in mice and rats by stimulating energy expenditure at the CNS level, possibly in the hypothalamus.
|
|
| 2. |
- Stenlöf, Kaj, 1965, et al.
(författare)
-
Interleukin-6 levels in the central nervous system are negatively correlated with fat mass in overweight/obese subjects.
- 2003
-
Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 88:9, s. 4379-83
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, we demonstrated that intracerebroventricular injection of IL-6 increases energy expenditure and decreases body fat in rodents. Therefore, IL-6 may play a role in appetite and body weight control in the central nervous system. In the present study we evaluated cerebrospinal fluid (CSF) and serum IL-6 levels in humans in relation to body fat content and to CSF and serum levels of leptin. Thirty-two healthy overweight/obese male subjects with a body mass index range of 29.3-36.0 kg/m(2) were studied. Total and sc body fat were measured by dual energy x-ray absorptiometry and computed tomography, respectively. CSF IL-6 levels were in some individuals higher than serum IL-6 levels and correlated negatively with total body weight, sc and total body fat. In contrast, CSF leptin levels were 30-60 times lower than serum leptin levels and correlated positively with serum leptin, body weight, sc and total body fat. Furthermore, there was a negative correlation between CSF IL-6 and leptin. In conclusion, CSF IL-6 differs in many ways from CSF leptin. CSF IL-6 may be locally produced rather than serum derived, and body fat-regulating regions in the central nervous system may be exposed to insufficient IL-6 levels in more severe obesity.
|
|
| 3. |
- Wallenius, Kristina, 1973, et al.
(författare)
-
Liver-derived IGF-I regulates GH secretion at the pituitary level in mice.
- 2001
-
Ingår i: Endocrinology. - 0013-7227. ; 142:11, s. 4762-70
-
Tidskriftsartikel (refereegranskat)abstract
- We have reported that liver-specific deletion of IGF-I in mice (LI-IGF-I-/-) results in decreased circulating IGF-I and increased GH levels. In the present study, we determined how elimination of hepatic IGF-I modifies the hypothalamic-pituitary GH axis to enhance GH secretion. The pituitary mRNA levels of GH releasing factor (GHRF) receptor and GH secretagogue (GHS) receptor were increased in LI-IGF-I-/- mice, and in line with this, their GH response to ip injections of GHRF and GHS was increased. Expression of mRNA for pituitary somatostatin receptors, hypothalamic GHRF, somatostatin, and neuropeptide Y was not altered in LI-IGF-I-/- mice, whereas hypothalamic IGF-I expression was increased. Changes in hepatic expression of major urinary protein and the PRL receptor in male LI-IGF-I-/- mice indicated an altered GH release pattern most consistent with enhanced GH trough levels. Liver weight was enhanced in LI-IGF-I-/- mice of both genders. In conclusion, loss of liver-derived IGF-I enhances GH release by increasing expression of pituitary GHRF and GHS receptors. The enhanced GH release in turn affects several liver parameters, in line with the existence of a pituitary-liver axis.
|
|
| 4. |
- Wallenius, Ville, 1970, et al.
(författare)
-
Interleukin-6-deficient mice develop mature-onset obesity.
- 2002
-
Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 8:1, s. 75-9
-
Tidskriftsartikel (refereegranskat)abstract
- The immune-modulating cytokine interleukin-6 (IL-6) is expressed both in adipose tissue and centrally in hypothalamic nuclei that regulate body composition. We investigated the impact of loss of IL-6 on body composition in mice lacking the gene encoding IL-6 (Il6-/- mice) and found that they developed mature-onset obesity that was partly reversed by IL-6 replacement. The obese Il6-/- mice had disturbed carbohydrate and lipid metabolism, increased leptin levels and decreased responsiveness to leptin treatment. To investigate the possible mechanism and site of action of the anti-obesity effect of IL-6, we injected rats centrally and peripherally with IL-6 at low doses. Intracerebroventricular, but not intraperitoneal IL-6 treatment increased energy expenditure. In conclusion, centrally acting IL-6 exerts anti-obesity effects in rodents.
|
|
| 5. |
- Wernstedt, Ingrid, 1978, et al.
(författare)
-
Increased levels of acylation-stimulating protein in interleukin-6-deficient (IL-6(-/-)) mice
- 2006
-
Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 147:6, s. 2690-5
-
Tidskriftsartikel (refereegranskat)abstract
- IL-6-deficient (IL-6(-/-)) mice develop obesity at 6-7 months of age. To elucidate the mechanisms of this mature-onset obesity, global gene expression profiles of 3-month-old preobese IL-6(-/-) were compared with those of IL-6(+/+) mice using DNA arrays. Genes that were up-regulated in IL-6(-/-) mice included the factors transthyretin and properdin in white adipose tissue and adipsin in muscle. These factors have been shown to influence the formation of acylation-stimulating protein (ASP), a cleavage product of complement C3. ASP stimulates the synthesis of triacylglycerol in adipocytes, and ASP-deficient mice are resistant to diet-induced obesity. In line with the increases in transthyretin, properdin, and adipsin, ASP levels in serum were increased by 31-54% in IL-6(-/-) compared with IL-6(+/+) mice. Furthermore, IL-6 replacement treatment in IL-6(-/-) mice decreased ASP levels significantly by 25-60%. In conclusion, ASP levels are increased in preobese IL-6(-/-) mice. This increase may result in increased triacylglycerol formation and uptake in IL-6(-/-) adipocytes and thereby contribute to the development of obesity in IL-6(-/-) mice.
|
|
| 6. |
- Agreus, L., et al.
(författare)
-
Significant over- and misuse of PPIs
- 2021
-
Ingår i: Lakartidningen. - 1652-7518. ; 118
-
Tidskriftsartikel (refereegranskat)abstract
- PPIs (Proton-pump inhibitors) offers the best treatment for acid related diseases. The predominant indications for PPI prescription are: GERD eradication of H. pylori-infection in combination with antibiotics H. pylori-negative peptic ulcer healing of and prophylaxis against NSAID/COXIB--induced gastroduodenal lesions acid hypersecretory states such as Zollinger-Ellisons syndrome. The market for PPIs continues to expand in most countries. A significant over- and misuse of PPIs prevails in hospital care as well as in general practice. The predominant reasons for and mechanisms behind the over- and misuse of PPIs are well recognised. The most important consequences of this overprescription of PPIs are increasing medical costs and risk for long-term adverse side effects. Continued education and dedicated information are key factors to guide physicians, medical personnel and patients to adopt to generally accepted principles for and balanced use of PPIs.
|
|
| 7. |
- Agreus, Lars, et al.
(författare)
-
Stor överförskrivning och ökat bruk av protonpumpshämmare : Utbildning och information är en nyckel till att vägleda läkare och allmänhet till rätt användning [Significant over- and misuse of PPIs]
- 2021
-
Ingår i: Läkartidningen. - Stockholm, Sweden : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 118
-
Tidskriftsartikel (refereegranskat)abstract
- PPIs (Proton-pump inhibitors) offers the best treatment for acid related diseases. The predominant indications for PPI prescription are:GERDeradication of H. pylori-infection in combination with antibioticsH. pylori-negative peptic ulcer healing of and prophylaxis against NSAID/COXIB--induced gastroduodenal lesions acid hypersecretory states such as Zollinger-Ellisons syndrome.The market for PPIs continues to expand in most countries. A significant over- and misuse of PPIs prevails in hospital care as well as in general practice. The predominant reasons for and mechanisms behind the over- and misuse of PPIs are well recognised. The most important consequences of this overprescription of PPIs are increasing medical costs and risk for long-term adverse side effects. Continued education and dedicated information are key factors to guide physicians, medical personnel and patients to adopt to generally accepted principles for and balanced use of PPIs.
|
|
| 8. |
- Benrick, Anna, 1979, et al.
(författare)
-
Interleukin-6 mediates exercise-induced increase in insulin sensitivity in mice.
- 2012
-
Ingår i: Experimental physiology. - : Wiley. - 1469-445X .- 0958-0670. ; 97:11 SI, s. 1224-1235
-
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.
|
|
| 9. |
- Bratlie, Svein-Olav, et al.
(författare)
-
Proteomic Approach to the Potential Role of Angiotensin II in Barrett Dysplasia
- 2019
-
Ingår i: Proteomics - Clinical Applications. - : Wiley. - 1862-8346 .- 1862-8354. ; 13:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Aim: Dysplasia in Barrett's esophagus (BE) is regarded as a preneoplastic lesion. The renin–angiotensin system (RAS), known for its role in electrolyte homeostasis and hemodynamics, has also been shown to have tissue-based features linked to proliferation, inflammation, and cancer. RAS is associated with BE dysplasia. The aim of this study is to investigate possible effects of the RAS in BE dysplasia by using RAS-interfering pharmaceutical agents and by assessment of global protein expression in esophageal mucosal biopsies. Methods: Endoscopic biopsies are taken from 18 BE in patients with low-grade dysplasia before and after 3 weeks of treatment with either angiotensin-converting enzyme inhibitors (enalapril 5 mg; n = 6) or angiotensin II receptor type 1 blockers (candesartan 8 mg; n = 6), or no treatment (n = 6). A global proteomics analysis by 2D gel electrophoresis and mass spectrometry (MS) is then performed to identify proteins that are regulated after interference with RAS. Results: Three proteins are identified to show significant modulation of expression 60 kDa heat shock protein (downregulated), protein disulfide isomerase A3 (downregulated), and inorganic pyrophosphatase (upregulated). Conclusion: Three proteins with no previously known links to esophageal RAS, but with possible relevance for the development of esophageal adenocarcinoma (EAC) are detected. Altered expression by interference with the RAS suggests an involvement of angiotensin II in the development of EAC in BE. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
|
|
| 10. |
- Börgeson, Emma, et al.
(författare)
-
AICAR ameliorates high-fat diet-associated pathophysiology in mouse and ex vivo models, independent of adiponectin.
- 2017
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 60:4, s. 729-739
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, we aimed to evaluate the therapeutic potential of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMP-activated protein kinase, for ameliorating high-fat diet (HFD)-induced pathophysiology in mice. We also aimed to determine whether the beneficial effects of AICAR were dependent on adiponectin. Furthermore, human adipose tissue was used to examine the effect of AICAR ex vivo.Six-week-old male C57BL/6J wild-type and Adipoq (-/-) mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12weeks and given vehicle or AICAR (500μg/g) three times/week from weeks 4-12. Diet-induced pathophysiology was examined in mice after 11 weeks by IPGTT and after 12 weeks by flow cytometry and western blotting. Human adipose tissue biopsies from obese (BMI 35-50kg/m(2)) individuals were incubated with vehicle or AICAR (1mmol/l) for 6h at 37°C, after which inflammation was characterised by ELISA (TNF-α) and flow cytometry.AICAR attenuated adipose inflammation in mice fed an HFD, promoting an M1-to-M2 macrophage phenotype switch, while reducing infiltration of CD8(+) T cells. AICAR treatment of mice fed an HFD partially restored glucose tolerance and attenuated hepatic steatosis and kidney disease, as evidenced by reduced albuminuria (p<0.05), urinary H2O2 (p<0.05) and renal superoxide levels (p<0.01) in both wild-type and Adipoq (-/-) mice. AICAR-mediated protection occurred independently of adiponectin, as similar protection was observed in wild-type and Adipoq (-/-) mice. In addition, AICAR promoted an M1-to-M2 macrophage phenotype switch and reduced TNF-α production in tissue explants from obese human patients.AICAR may promote metabolic health and protect against obesity-induced systemic diseases in an adiponectin-independent manner. Furthermore, AICAR reduced inflammation in human adipose tissue explants, suggesting by proof-of-principle that the drug may reduce obesity-induced complications in humans.ClinicalTrials.gov NCT02322073.
|
|
