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Aims/hypothesis: Low-grade inflammation is a feature of chronic diseases such as type 2 diabetes and lipodystrophy. It is associated with abdominal adiposity, increased levels of NEFA, hyperinsulinaemia and low adiponectin levels. However, the causal relationship between impaired metabolism and inflammation is not understood. We explored the anti-lipolytic effect of acipimox and insulin on adiponectin and adipocyte-associated cytokines in patients with lipodystrophy. Methods: In a randomised placebo-controlled crossover design using nine patients with non-diabetic, HIV-associated lipodystrophy, we assessed whether (1) overnight administration of a low dose of acipimox and/or (2) insulin-induced suppression of NEFA flux altered circulating plasma levels of adiponectin, IL-18, TNF-α and IL-6 in the basal condition and in a two-stage euglycaemic-hyperinsulinaemic clamp combined with stable isotopes (insulin infusion rates 20 mU m min and 50 mU m min). Results: Insulin decreased plasma NEFA in a dose-dependent manner ( p < 0.0001). Acipimox reduced basal plasma NEFAs and plasma NEFAs during the low-dose insulin infusion compared with placebo ( p < 0.0001 for acipimox effect). Plasma adiponectin and plasma IL-18 were reduced during both situations where lipolysis was inhibited ( p < 0.0001 for acipimox effect; p < 0.0001 and p < 0.05 for insulin effect on plasma adiponectin and plasma IL-18, respectively). In contrast, plasma IL-6 and plasma TNF-α did not change during low NEFA concentrations. Conclusions/interpretation: Using two different tools to manipulate lipolysis, the present study found that acute inhibition of lipolysis reduces levels of adiponectin and IL-18 in patients with HIV-associated lipodystrophy. [ABSTRACT FROM AUTHOR]

Objective:To determine the effect of obesity without the confounding effect of metabolic complications on the lipoprotein subclass profile in men and women.Design:Cross-sectional study.Subjects:A total of 40 lean (body mass index (BMI): 18.5–25 kg/m2) and 40 obese (BMI: 30–45 kg/m2) subjects, with blood pressure <140/90 mm Hg, fasting plasma glucose concentration <100 mg per 100 ml and total triglyceride concentration <150 mg per 100 ml; all obese subjects had normal oral glucose tolerance.Measurements:Fasting concentrations of very low-, intermediate-, low- and high-density lipoproteins (VLDL, IDL, LDL, and HDL, respectively) and average VLDL, LDL and HDL particle sizes were evaluated by using proton nuclear magnetic resonance spectroscopy.Results:Obese compared with lean individuals of both sexes had increased plasma concentrations of VLDL (by ∼50%), IDL (by ∼100%), LDL (by ∼50%), and to some extent HDL (by ∼10%) particles (P<0.05). The contribution of large VLDL to total VLDL concentration, small LDL to total LDL concentration, and small HDL to total HDL concentration was greater in obese than lean subjects (P<0.05), resulting in larger average VLDL size but smaller average LDL and HDL sizes (P<0.05). Women, compared with men, had reduced concentrations of total VLDL particles (by ∼10%) due to lower concentrations of large and medium VLDL and a shift toward large at the expense of small HDL particles (P<0.05), with no difference in total HDL particle concentration. IDL and total LDL concentrations and LDL subclass distribution were not different between men and women.Conclusion:Obesity is associated with pro-atherogenic alterations in the lipoprotein subclass profile, which may increase cardiovascular disease risk even in the absence of classical metabolic risk factors. On the other hand, the female cardiovascular disease risk advantage is probably largely related to differences in traditional lipid risk factors (plasma triglyceride and HDL-cholesterol concentrations) because sex differences in the plasma lipoprotein subclass profile are minimal.International Journal of Obesity (2008) 32, 1655–1664; doi:10.1038/ijo.2008.164; published online 9 September 2008 [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is associated with increased whole body protein breakdown and low-grade systemic inflammation. We aimed to determine if physical training of patients with COPD induces anti-inflammatory effects and decreases whole-body protein breakdown. Nineteen subjects with severe (FEV1=31±1) COPD were randomized into a training group ( n=9) and a control group ( n=10). Twenty healthy subjects were studied for baseline comparison. The “COPD training” group participated in an outpatient rehabilitation program consisting of endurance training (walking at 85% of VO2max) twice weekly for 7 weeks plus daily home-based training. Maximum walking distance increased by almost 70% in the training group after 7 weeks of training. At baseline, the concentrations of C-reactive protein (CRP) and IL-18 in plasma were increased in subjects with COPD compared with healthy subjects ( P<0.05) and leucine rate of appearance ( Ra) was ∼15% greater ( P<0.05) in subjects with COPD. Training had no effect on the plasma concentration of inflammatory markers but decreased leucine Ra in subjects with COPD by ∼10% ( P<0.05). In conclusion, 7 weeks of physical training markedly improved endurance in patients with COPD and accelerated whole-body protein breakdown in patients with COPD was attenuated by physical training independent of changes in inflammatory markers. [ABSTRACT FROM AUTHOR]

In many animals the rate of protein synthesis is higher in slow-twitch, oxidative than fast-twitch, glycolytic muscles. To discover if muscles in the human body also show such differences, we measured[13C]leucine incorporation into proteins of anatomically distinct muscles of markedly different fibre-type composition (vastus lateralis, triceps, soleus) after an overnight fast and during infusion of a mixed amino acid solution (75 mg amino acids kg−1 h−1) in nine healthy, young men. Type-1 fibres contributed 83± 4% (mean±s.e.m.) of total fibres in soleus, 59± 3% in vastus lateralis and 22± 2% in triceps. The basal myofibrillar and sarcoplasmic protein fractional synthetic rates (FSR, % h−1) were 0.034± 0.001 and 0.064± 0.001 (soleus), 0.031± 0.001 and 0.060± 0.001 (vastus), and 0.027± 0.001 and 0.055± 0.001 (triceps). During amino acid infusion, myofibrillar protein FSR increased to 3-fold, and sarcoplasmic to 2-fold basal values (P<0.001). The differences between muscles, although significant statistically (tricepsversussoleus and vastus lateralis,P<0.05), were within∼15%, biologically probably insignificant. The rates of collagen synthesis were not affected by amino acid infusion and varied by<5% between muscles and experimental conditions. [ABSTRACT FROM AUTHOR]

Hypertriglyceridemia is common in individuals with human immunodeficiency (HIV) infection, but the mechanisms responsible for increased plasma triglyceride (TG) concentrations are not clear. We evaluated fatty acid and VLDL-TG kinetics during basal conditions and during a glucose infusion that resulted in typical postprandial plasma glucose and insulin concentrations in six men with HIV-dyslipidemia [body mass index (BMI): 28 ± 2 kg/m²] and six healthy men (BMI: 26 ± 2 kg/m²). VLDL-TG secretion and palmitate rate of appearance (R[sub a]) in plasma were measured by using stable-isotope-labeled tracer techniques. Basal palmitate R[sub a] and VLDL-TG secretion rates were greater (P < 0.01 for both) in men with HIV-dyslipidemia (1.04 ± 0.07 µmol palmitate·kg[sup -1]·.min[sup -1] and 5.7 ± 0.6 µmol VLDL-TG·1 plasma[sup -1]·min[sup -1]) than in healthy men (0.67 ± 0.08 µmol palmitate·kg[sup -1]·min[sup -1] and 3.0 ± 0.5 µmol VLDL-TG·1 plasma[sup -1]·main[sup -1]). Basal VLDL-TG plasma clearance was lower in men with HIV dyslipidemia (13 ± 1 ml/min) than in healthy men (19 ± 2 ml/min; P < 0.05). Glucose infusion decreased palmitate R[sub a] (by ∼50%) and the VLDL-TG secretion rate (by ∼30%) in both groups, but the VLDL-TG secretion rate remained higher (P < 0.05) in subjects with HIV-dyslipidemia. These findings demonstrate that increased secretion of VLDL-TG and decreased plasma VLDL-TG clearance, during both fasting and fed conditions, contribute to hypertriglyceridemia in men with HIV-dyslipidemia. Although it is likely that increased free fatty acid release from adipose tissue contributes to the increase in basal VLDL-TG concentration, other factors must be involved, because insulin-induced suppression of lipolysis and systemic fatty acid availability did not normalize the VLDL-TG secretion rate. [ABSTRACT FROM AUTHOR]

Presents information on a study which determined the availability of dietary glutamine for skeletal muscle and its effects on muscle glutamine concentration in healthy subjects. Methodology; Results of the study; Discussion.

Provides information on a study which quantifies splanchnic and leg acetate metabolism in human volunteers. Experimental design and procedures; Interpretation of acetate kinetics; Conclusions.