Interleukin-6 production in human subcutaneous abdominal adipose tissue: the effect of exercise. (1/417)

The interleukin-6 (IL-6) output from subcutaneous, abdominal adipose tissue was studied in nine healthy subjects before, during and for 3 h after 1 h two-legged bicycle exercise at 60 % maximal oxygen consumption. Seven subjects were studied in control experiments without exercise. The adipose tissue IL-6 output was measured by direct Fick technique. An artery and a subcutaneous vein on the anterior abdominal wall were catheterized. Adipose tissue blood flow was measured using the 133Xe-washout method. In both studies there was a significant IL-6 output in the basal state and no significant change was observed during exercise. Post-exercise the IL-6 output began to increase after 30 min. Three hours post-exercise it was 58.6 +/- 22.2 pg (100 g)(-1) min(-1). In the control experiments the IL-6 output also increased, but it only reached a level of 3.5 +/- 0.8 pg (100 g)(-1) min(-1). The temporal profile of the post-exercise change in the IL-6 output closely resembles the changes in the outputs of glycerol and fatty acids, which we have described previously in the same adipose tissue depot. The difference is that it begins to increase ~30 min before the glycerol and fatty acid outputs begin to increase. Thus, we suggest that the enhanced IL-6 production post-exercise in abdominal, subcutaneous adipose tissue may act locally via autocrine/paracrine mechanisms influencing lipolysis and fatty acid mobilization rate from this lipid depot.  (+info)

Metabolic effects of interleukin-6 in human splanchnic and adipose tissue. (2/417)

Interleukin-6 (IL-6) was infused intravenously for 2.5 h in seven healthy human volunteers at a dose giving rise to a circulating IL-6 concentration of approximately 35 ng l(-1). The metabolic effects of this infusion were studied in subcutaneous adipose tissue on the anterior abdominal wall and in the splanchnic tissues by the Fick principle after catheterizations of an artery, a subcutaneous vein draining adipose tissue, and a hepatic vein, and measurements of regional adipose tissue and splanchnic blood flows. In control studies without IL-6 infusion subcutaneous adipose tissue metabolism was studied by the same technique in eight healthy subjects. The net release of glycerol and fatty acids from the subcutaneous abdominal adipose tissue remained constant in the control experiment. IL-6 infusion gave rise to increase in net glycerol release in subcutaneous adipose tissue while the net release of fatty acids did not change significantly. In the splanchnic region IL-6 elicited a pronounced vasodilatation, and the uptake of fatty acids and the gluconeogenic precursors glycerol and lactate increased significantly. The splanchnic net output of glucose and triacylglycerol did not change during the IL-6 infusion. It is concluded that IL-6 elicits lipolytic effects in human adipose tissue in vivo, and that IL-6 also has effects on the splanchnic lipid and carbohydrate metabolism.  (+info)

Effects of weight loss on changes in insulin sensitivity and lipid concentrations in premenopausal African American and white women. (3/417)

BACKGROUND: Few studies have tested the hypothesis that changes in disease risk factors are more closely associated with changes in visceral fat than with changes in other adipose tissue depots, particularly in subjects with different ethnic or racial backgrounds. OBJECTIVE: We describe changes in triacylglycerol, total cholesterol, HDL cholesterol, LDL cholesterol, insulin sensitivity (S(i)), visceral fat, and subcutaneous abdominal adipose tissue (SAAT) with weight loss in premenopausal, overweight [body mass index (in kg/m(2)): 27-30], African American (n = 19) and white (n = 18) women. DESIGN: Assessments were performed before and after diet-induced weight loss to a BMI < 25. Body composition and body fat distribution were assessed with dual-energy X-ray absorptiometry and computed tomography, respectively; S(i) was assessed with an intravenous-glucose-tolerance test and minimal modeling. RESULTS: White women lost significantly more visceral fat and less SAAT than did African American women despite similar weight losses (approximately 13 kg). Mixed-model analysis indicated significant effects of time (ie, weight loss) on S(i), triacylglycerol, HDL cholesterol, and LDL cholesterol and of race on triacylglycerol. Time x race interaction terms were not significant. After adjustment for either total body or visceral fat, time was not related to any outcome variable; however, race remained significantly related to triacylglycerol. CONCLUSIONS: With weight loss, moderately overweight African American and white women experienced significant improvements in S(i) and lipids. The beneficial effects of weight loss did not differ with race and could not be attributed to a specific body fat depot. Lower triacylglycerol concentrations among African American women are independent of both obesity status and body fat distribution.  (+info)

FOXC2 mRNA Expression and a 5' untranslated region polymorphism of the gene are associated with insulin resistance. (4/417)

The human transcription factor FOXC2 has recently been shown to protect against diet-induced insulin resistance in transgenic mice. We investigated the expression of FOXC2 in fat and muscle and performed a genetic analysis in human subjects. FOXC2 mRNA levels were increased in visceral compared with subcutaneous fat from obese subjects (12 +/- 4-fold; P = 0.0001), and there was a correlation between whole-body insulin sensitivity and FOXC2 mRNA levels in visceral fat (fS-insulin R = -0.64, P = 0.01, and homeostasis model assessment of insulin resistance [HOMA-IR] R = -0.68, P = 0.007) and skeletal muscle (fS-insulin R = -0.57, P = 0.03, and HOMA-IR R = -0.55, P = 0.04). Mutation screening of the FOXC2 gene identified a common polymorphism in the 5' untranslated region (C-512T). The T allele was associated with enhanced insulin sensitivity (HOMA-IR P = 0.007) and lower plasma triglyceride levels in females (P = 0.007). Also, the higher expression of FOXC2 in visceral than in subcutaneous fat was restricted to subjects homozygous for the T allele (P = 0.03 vs. P = 0.7). Our data suggest that increased FOXC2 expression may protect against insulin resistance in human subjects and that genetic variability in the gene may influence features associated with the metabolic syndrome.  (+info)

Relief of inflammatory pain in rats by local use of the selective P2X7 ATP receptor inhibitor, oxidized ATP. (5/417)

OBJECTIVE: Oxidized ATP (oATP) is a selective inhibitor of the P2Z/P2X7 ATP receptor for extracellular ATP, which contributes to the antinociceptive effect. This study sought to determine the mechanism by which local administration of oATP is able to relieve inflammatory pain in arthritic rat paws. METHODS: Arthritis was induced in Wistar rats by injections of Freund's complete adjuvant into one hind paw. Nociceptive thresholds were measured before and after local injection of oATP into the inflamed paws. The influence on pain transmission due to the presence of recruited inflammatory cells at the site of inflammation was determined by inhibiting the initial phase of their migration (by intravenous treatment with fucoidin, which blocks the adhesion molecules of the selectin family). ATP intraplantar content was determined in the different experimental conditions. Histologic features of the hind paws were evaluated by using the anti-P2X7 receptor polyclonal antibody. RESULTS: Intraplantar administration of oATP into inflamed paws significantly relieved inflammatory pain. The antinociceptive effect of oATP was independent of the immune-cell recruitment. ATP levels in inflamed tissues were significantly reduced by oATP treatment. A variable presence of P2X7 receptors on cutaneous sensory nerves with respect to the different treatments was observed. Following oATP treatment, there was a reduction in P2X7 expression in the endings of peripheral nerves, as well as in endothelial cells. CONCLUSION: Oxidized ATP inhibits inflammatory pain in arthritic rats by inhibition of the P2X7 receptor for ATP, which is localized on nerve terminals.  (+info)

Regulation of plasma PAI-1 concentrations in HAART-associated lipodystrophy during rosiglitazone therapy. (6/417)

OBJECTIVE: Patients with highly active antiretroviral therapy-associated lipodystrophy (HAART+LD+) have high plasminogen activator inhibitor-1 (PAI-1) concentrations for unknown reasons. We determined whether (1). plasma PAI-1 antigen concentrations are related to liver fat content (LFAT) independently of the size of other fat depots and (2) rosiglitazone decreases PAI-1 and LFAT in these patients. METHODS AND RESULTS: In the cross-sectional study, 3 groups were investigated: 30 HIV-positive patients with HAART+LD+, 13 HIV-positive patients without lipodystrophy (HAART+LD-), and 15 HIV-negative subjects (HIV-). In the treatment study, the HAART+LD+ group received either rosiglitazone (8 mg, n=15) or placebo (n=15) for 24 weeks. Plasma PAI-1 was increased in HAART+LD+ (28+/-2 ng/mL) compared with the HAART+LD- (18+/-3, P<0.02) and HIV- (10+/-3, P<0.001) groups. LFAT was higher in HAART+LD+ (7.6+/-1.7%) than in the HAART+LD- (2.1+/-1.1%, P<0.001) and HIV- (3.6+/-1.2%, P<0.05) groups. Within the HAART+LD+ group, plasma PAI-1 was correlated with LFAT (r=0.49, P<0.01) but not with subcutaneous or intra-abdominal fat or serum insulin or triglycerides. In subcutaneous adipose tissue, PAI-1 mRNA was 2- to 3-fold higher in the HAART+LD+ group than in either the HAART+LD- or HIV- group. Rosiglitazone decreased LFAT, serum insulin, and plasma PAI-1 and increased serum triglycerides but had no effect on intra-abdominal or subcutaneous fat mass or PAI-1 mRNA. CONCLUSIONS: Plasma PAI-1 concentrations are increased in direct proportion to LFAT in HAART+LD+ patients. Rosiglitazone decreases LFAT, serum insulin, and plasma PAI-1 without changing the size of other fat depots or PAI-1 mRNA in subcutaneous fat. These data suggest that liver fat contributes to plasma PAI-1 concentrations in these patients.  (+info)

Endogenous interleukin-10 is required for the defervescence of fever evoked by local lipopolysaccharide-induced and Staphylococcus aureus-induced inflammation in rats. (7/417)

We tested the hypothesis that endogenous interleukin (IL)-10 limits the fever induced by a Gram-negative bacterial toxin (Escherichia coli lipopolysaccharide, LPS) and a Gram-positive bacterial toxin (Staphylococcus aureus), when these toxins are injected into a subcutaneous air pouch (I.PO.) in rats. Injection of LPS or S. aureus caused fevers that were reduced in amplitude and duration by simultaneous administration of rat recombinant IL-10. The inhibition of fever by IL-10 was accompanied by a significant reduction in the toxin-evoked increases in concentrations of immunoreactive IL-6 at the site of inflammation and of IL-6 and IL-1 receptor antagonist in the circulation. Conversely, neutralisation of endogenous IL-10 in the pouch increased the amplitude and dramatically increased the duration of toxin-evoked fever, and augmented toxin-induced increases in pouch tumour necrosis factor-alpha, IL-1beta, and especially IL-6. Our data support a crucial regulatory role for endogenous IL-10 in limiting the fever responses during both Gram-negative and Gram-positive infections.  (+info)

Opposite nociceptive effects of the arginine/NO/cGMP pathway stimulation in dermal and subcutaneous tissues. (8/417)

1. Nitric oxide has been described either as pronociceptive or antinociceptive. In this investigation, using an electronic pressure-metre, the intradermal and the subcutaneous effects of prostaglandin E(2) (PGE(2)) and agents that mimic or inhibit the arginine/NO/cGMP pathway were compared. 2. The hypernociceptive effect of the intradermal injection of PGE(2) (100 ng) was immediate, peaking within 15-30 min and returning to basal values in 45-60 min. The subcutaneous injection of PGE(2) induced a hypernociception with a delayed peak (3 h) plateauing for 4-6 h. 3. Intradermal administration of 3-morpholino-sydnonimine-hydrochloride (SIN-1) enhanced, while its subcutaneous administration inhibited, subcutaneous hypernociception induced by PGE(2). This inhibition was prevented by ODQ (8 micro g) but not by NG-monomethyl-L-arginine (L-NMMA) (50 micro g). 4. Intradermal but not subcutaneous administration of L-arginine (1-100 micro g), SIN-1 (1-100 micro g) and dibutyrylguanosine 3':5'-cyclic monophosphate (db cGMP) (0.1-100 micro g) induced an early (15-30 min) dose-dependent hypernociceptive effect. Intradermal pretreatment with NG-monomethyl-L-arginine (L-NMMA; 50 micro g) inhibited the hypernociception induced by L-Arg (10 micro g), but not that induced by SIN-1 (10 micro g) or db cGMP (10 micro g). 5. Intradermal injection of ODQ (8 micro g) antagonized the hypernociception induced by L-arginine and SIN-1, but not that induced by db cGMP. 6. Considering (a) the different time course of intradermal and subcutaneous PGE(2)-induced hypernociception, (b) the opposite nociceptive effect of intradermal and subcutaneous administration of SIN-1 (db cGMP) as well as the arginine/NO/cGMP pathway, the existence of different subsets of nociceptive primary sensory neurons in which the arginine/NO/cGMP pathway plays opposing roles is suggested. This hypothesis would explain the apparent contradictory observations described in the literature.  (+info)