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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 [+ or -] 2 kg/[m.sup.2]] and six healthy men (BMI: 26 [+ or -] 2 kg/[m.sup.2]). 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 [+ or -] 0.07 [micro]mol palmitate*[kg.sup.-1].[min.sup.-1] and 5.7 [+ or -] 0.6 [micro]mol VLDL-TG*l [plasma.sup.-1]*[min.sup.-1]) than in healthy men (0.67 [+ or -] 0.08 [micro]mol palmitate*[kg.sup.-1]*[min.sup.-1] and 3.0 [+ or -] 0.5 [micro]mol VLDL-TG*l [plasma.sup.-1]*[min.sup.-1]). Basal VLDL-TG plasma clearance was lower in men with HIV-dyslipidemia (13 [+ or -]1 ml/min) than in healthy men (19 [+ or -] 2 ml/min; P < 0.05). Glucose infusion decreased palmitate [R.sup.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. stable isotopes; lipolysis; hypertriglyceridemia; metabolism; human immunodeficiency virus

Research was conducted to examine regional acetate kinetics and oxidation in human subjects. To examine splanchnic and leg acetate metabolism, five fasted human volunteers were given a 3-h primed continuous infusion of (1,2(super 13C))acetate. To test for whole body labeled carbon recovery, three volunteers were given (1,2-(super 13C))acetate infusion for 15 h. It was observed that whole body acetate carbon recovery in CO2 was substantially higher after a 15-h infusion. Results indicate that the leg rapidly absorbs acetate and carbon recovery depends on infusion time.

Whole body and skeletal muscle glutamine metabolism in healthy subjects. Am J Physiol Endocrinol Metab 280: E323-E333, 2001.--We measured glutamine kinetics using L-[5-[sup.15]N]glutamine and L-[ring-[sup.2][H.sub.5]]phenylalanine infusions in healthy subjects in the postabsorptive state and during ingestion of an amino acid mixture that included glutamine, alone or with additional glucose. Ingestion of the amino acid mixture increased arterial glutamine concentrations by ~20% (not by 30%; P [is less than] 0.05), irrespective of the presence or absence of glucose. Muscle free glutamine concentrations remained unchanged during ingestion of amino acids alone but decreased from 21.0 [+ or -] 1.0 to 16.4 [+ or -] 1.6 mmol/l (P [is less than] 0.05) during simultaneous ingestion of glucose due to a decrease in intramuscular release from protein breakdown and glutamine synthesis (0.82 [+ or -] 0.10 vs. 0.59 [+ or -] 0.06 [micro]mol [multiplied by] 100 ml [leg.sup.-1] [multiplied by] [min.sup.-1]; P [is less than] 0.05). In both protocols, muscle glutamine inward and outward transport and muscle glutamine utilization for protein synthesis increased during amino acid ingestion; leg glutamine net balance remained unchanged. In summary, ingestion of an amino acid mixture that includes glutamine increases glutamine availability and uptake by skeletal muscle in healthy subjects without causing an increase in the intramuscular free glutamine pool. Simultaneous ingestion of glucose diminishes the intramuscular glutamine concentration despite increased glutamine availability in the blood due to decreased glutamine production. transport; synthesis; stable isotopes; protein; amino acid; glucose

To gain insight into the mechanisms regulating plasma lipid homeostasis, FFA, VLDL-triglyceride (TG), and VLDL-apolipoprotein B-100 (apoB-100) kinetics are commonly assessed using stable isotope-labeled tracer methods. The reproducibility of these measurements, which is critical for the experimental design, is unknown. Therefore, we investigated the repeatability of plasma FFA, VLDL-TG, and VLDL-apoB-100 kinetics in eight healthy men using stable isotope-labeled tracer techniques. There were no systematic differences in plasma FFA, VLDL-TG, and VLDL-apoB-100 concentrations and kinetics between the two studies. Intraindividual day-to-day variability for various outcome variables ranged from 15% to 25%, and almost all of this was of biological origin. The most robust outcome variables were FFA rate of appearance and hepatic VLDL-TG and VLDL-apoB-100 secretion rates; the least robust were VLDL-TG and VLDL-apoB-100 plasma clearance rates and mean residence times. Overall, physiologically meaningful differences in mean values (i.e., 25–30% in magnitude) can be obtained with a sample size of 6–10 subjects for paired studies and 12–20 subjects per group for cross-sectional studies, assuming a type I error rate of 0.05 and a type II error rate of 0.20 (i.e., 80% power). These findings will be useful for future studies investigating FFA, VLDL-TG, and VLDL-apoB-100 kinetics with the methods described.

Abstract Background Although there appear to be no differences in muscle protein turnover in young and middle aged men and women, we have reported significant differences in the rate of muscle protein synthesis between older adult men and women. This suggests that aging may affect muscle protein turnover differently in men and women. Methods We measured the skeletal muscle protein fractional synthesis rate (FSR) by using stable isotope-labeled tracer methods during basal postabsorptive conditions and during a hyperaminoacidemic-hyperinsulinemic-euglycemic clamp in eight young men (25–45 y), ten young women (25–45 y), ten old men (65–85 y) and ten old women (65–85 y). Results The basal muscle protein FSR was not different in young and old men (0.040 ± 0.004 and 0.043 ± 0.005%·h-1, respectively) and combined insulin, glucose and amino acid infusion significantly increased the muscle protein FSR both in young (to 0.063 ± 0.006%·h-1) and old (to 0.051 ± 0.008%·h-1) men but the increase (0.023 ± 0.004 vs. 0.009 ± 0.004%·h-1, respectively) was ~60% less in the old men (P = 0.03). In contrast, the basal muscle protein FSR was ~30% greater in old than young women (0.060 ± 0.003 vs. 0.046 ± 0.004%·h-1, respectively; P -1 vs. 0.072 ± 0.006%·h-1, respectively). Conclusions There is sexual dimorphism in the age-related changes in muscle protein synthesis and thus the metabolic processes responsible for the age-related decline in muscle mass.

Bariatric surgery in obese patients is a highly effective method of preventing or resolving type 2 diabetes mellitus (T2DM); however, the remission rate is not the same among different surgical procedures. We compared the effects of 20% weight loss induced by laparoscopic adjustable gastric banding (LAGB) or Roux-en-Y gastric bypass (RYGB) surgery on the metabolic response to a mixed meal, insulin sensitivity, and β cell function in nondiabetic obese adults. The metabolic response to meal ingestion was markedly different after RYGB than after LAGB surgery, manifested by rapid delivery of ingested glucose into the systemic circulation, by an increase in the dynamic insulin secretion rate, and by large, early postprandial increases in plasma glucose, insulin, and glucagon-like peptide-1 concentrations in the RYGB group. However, the improvement in oral glucose tolerance, insulin sensitivity, and overall β cell function after weight loss were not different between surgical groups. Additionally, both surgical procedures resulted in a similar decrease in adipose tissue markers of inflammation. We conclude that marked weight loss itself is primarily responsible for the therapeutic effects of RYGB and LAGB on insulin sensitivity, β cell function, and oral glucose tolerance in nondiabetic obese adults. [ABSTRACT FROM AUTHOR]

Objective: This study investigated how obesity, BMI ≥ 30 kg/m 2 , abdominal adiposity, and systemic inflammation relate to neuroinflammation using diffusion basis spectrum imaging., Methods: We analyzed data from 98 cognitively normal midlife participants (mean age: 49.4 [SD 6.2] years; 34 males [34.7%]; 56 with obesity [57.1%]). Participants underwent brain and abdominal magnetic resonance imaging (MRI), blood tests, and amyloid positron emission tomography (PET) imaging. Abdominal visceral and subcutaneous adipose tissue (VAT and SAT, respectively) was segmented, and Centiloids were calculated. Diffusion basis spectrum imaging parameter maps were created using an in-house script, and tract-based spatial statistics assessed white matter differences in high versus low BMI values, VAT, SAT, insulin resistance, systemic inflammation, and Centiloids, with age and sex as covariates., Results: Obesity, high VAT, and high SAT were linked to lower axial diffusivity, reduced fiber fraction, and increased restricted fraction in white matter. Obesity was additionally associated with higher hindered fraction and lower fractional anisotropy. Also, individuals with high C-reactive protein showed lower axial diffusivity. Higher restricted fraction correlated with continuous BMI and SAT particularly in male individuals, whereas VAT effects were similar in male and female individuals., Conclusions: The findings suggest that, at midlife, obesity and abdominal fat are associated with reduced brain axonal density and increased inflammation, with visceral fat playing a significant role in both sexes., (© 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Objective: To evaluate total, insulin-mediated, and non-insulin-mediated glucose disposal (TGD, IMGD, and NIMGD) after ingesting glucose in people with obesity and different glycemic status., Research Design and Methods: We developed and validated a new glucose tracer model in conjunction with an oral glucose tolerance test to determine IMGD, NIMGD, and TGD (sum of IMGD and NIMGD) after glucose ingestion in four groups of people: 1) lean with normal glucose tolerance (NGT), 2) obese with insulin resistance and NGT due to hyperinsulinemia (Ob-NGT group), 3) obese with insulin resistance and impaired glucose tolerance (IGT) due to inadequate hyperinsulinemia (Ob-IGT group), and 4) obese with insulin resistance and type 2 diabetes due to marked insulin insufficiency (Ob-T2D group). In addition, we evaluated the effect of intensive lifestyle therapy (ILT) that caused ∼15% weight loss on IMGD and NIMGD in people with obesity and type 2 diabetes (T2D)., Results: IMGD progressively decreased and NIMGD progressively increased from lean to Ob-NGT to Ob-IGT to Ob-T2D. IMGD accounted for about 70%, 65%, 50%, and 20% of TGD, and NIMGD accounted for ∼40%, 35%, 50%, and 80% of TGD in lean, Ob-NGT, Ob-IGT and Ob-T2D, respectively. Although NIMGD was approximately twofold and approximately threefold higher in Ob-IGT and Ob-T2D compared with Ob-NGT, NIMGD only partially compensated for markedly impaired IMGD in the Ob-IGT and Ob-T2D. ILT in people with obesity and T2D increased IMGD and decreased NIMGD., Conclusions: NIMGD is a major mechanism of postprandial TGD in people with insulin resistance and inadequate insulin secretion., (© 2024 by the American Diabetes Association.)

Observational studies have shown correlations between intramyocellular lipid (IMCL) content and muscle strength and contractile function in people with metabolically abnormal obesity. However, a clear physiologic mechanism for this association is lacking, and causation is debated. We combined immunofluorescent confocal imaging with force measurements on permeabilized muscle fibers from metabolically normal and metabolically abnormal mice and people with metabolically normal (defined as normal fasting plasma glucose and glucose tolerance) and metabolically abnormal (defined as prediabetes and type 2 diabetes) overweight/obesity to evaluate relationships among myocellular lipid droplet characteristics (droplet size and density) and biophysical (active contractile and passive viscoelastic) properties. The fiber type specificity of lipid droplet parameters varied by metabolic status and by species. It was different between mice and people across the board and different between people of different metabolic status. However, despite considerable quantities of IMCL in the metabolically abnormal groups, there were no significant differences in peak active tension or passive viscoelasticity between the metabolically abnormal and control groups in mice or people. Additionally, there were no significant relationships among IMCL parameters and biophysical variables. Thus, we conclude that IMCL accumulation per se does not impact muscle fiber biophysical properties or physically impede contraction., (© 2024 by the American Diabetes Association.)