The goal of this research is to establish a methodology to actively control a pneumatically driven robotic device that can induce specific muscle force patterns in target muscles during a subject's ...voluntary movement. In this paper, the generation of constant forces in the rectus femoris muscle throughout the knee extension, i.e., isotonic contractions, was studied. Due to a highly nonlinear nature of mapping the joint torque to muscle force, a simple application of constant torques to the knee joint would not realize isotonic contractions. The proposed robotic exercise accounted for nonlinear moment arms of muscles as functions of joint angles and nonlinear coordination of multiple muscles in the neuromuscular system to accomplish individual muscle control. A pneumatically powered one degree-of-freedom device that can impose active force feedback control has been designed and built. An exercise-planning algorithm has been developed that involved a musculoskeletal model of the lower body, and the dynamics of a pneumatic actuator. Five constant force profiles were tested for 20 healthy volunteers and electromyographic signals were collected while the device was applying calculated force profiles.
To evaluate the hypothesis that lipid oxidation predominates in postexercise recovery, we examined healthy men (n = 6; age = 21.2 +/- 0.6 yr) and women (n = 6; age = 22.8 +/- 2.1 yr) during and after ...two exercise tasks 89 min at 45% and 60 min at 65% of peak rate of oxygen consumption (V(O2 peak)) as well as a time-matched resting control trial (Con). Exercise bouts were matched for energy expenditure. Respiratory exchange ratios (RER) during exercise at 65% V(O2 peak) for both men and women (0.95 +/- 0.01 and 0.93 +/- 0.02) were significantly higher than 45% V(O2 peak) (0.89 +/- 0.01 and 0.86 +/- 0.02) and Con trials (0.86 +/- 0.01 and 0.86 +/- 0.02, respectively). During recovery, for men RER values were 0.78 +/- 0.01 and 0.76 +/- 0.01 after 45% and 65% exercise, respectively. For women, values were 0.79 +/- 0.01 and 0.78 +/- 0.01. These were significantly lower than during both the preexercise resting period and the corresponding no-exercise Con period (0.82 +/- 0.01 and 0.83 +/- 0.01, mean RER for men and women, respectively). Hence, the contribution of lipid oxidation to energy supply increased significantly during recovery compared with preexercise levels, and it was greater after exercise than during the time-matched, no-exercise Con period. It is concluded that, although carbohydrate is the major fuel source during moderate- to high-intensity exercise, 1) there is substantial postexercise lipid oxidation; and 2) lipid oxidation is the same during postexercise recovery whether the relative power output is 45% or 65% of V(O2 peak) when energy expenditure of exercise is matched.
Precise regulation of hepatic triglyceride (TG) metabolism and secretion is critical for health, and exercise could play a significant role. We compared one session of high-intensity interval ...exercise (HIIE) vs. continuous exercise (CE) on hepatic TG metabolism. Female and male mice were assigned to CE, HIIE, or sedentary control (CON). HIIE was a 30-min session of 30-s running intervals (30 m/min) interspersed with 60-s walking periods (5 m/min). CE was a distance- and duration-matched run at 13.8 m/min. Hepatic content of TG and TG secretion rates, as well as expression of relevant genes/proteins, were measured at 3 h (day 1) and 28 h (day 2) postexercise. On day 1, hepatic TG in CE and HIIE were both elevated vs. CON in both sexes with an approximately twofold greater elevation in HIIE vs. CE in females. In both sexes, hepatic perilipin 2 (PLIN2) protein on day 1 was increased significantly by both exercise types with a significantly greater increase with HIIE than CE, whereas the increase in mRNA reached significance only after HIIE. On day 2 in both sexes the increases in hepatic TG and PLIN2 with exercise declined toward CON levels. Only HIIE on day 2 resulted in reduced hepatic TG secretion by ∼20% in females with no effect in males. Neither exercise modality altered AMPK signaling or microsomal triglyceride transfer protein expression. Females exhibited higher hepatic TG secretion than males in association with different expression levels of related metabolic enzymes. These intensity-dependent and sex-specific alterations following exercise may have implications for sex-based exercise prescription.
The senescence accelerated SAMP8 mouse is a model for sarcopenia and provides an opportunity to study the effects of lifelong dietary composition on the loss of physical function with age. We studied ...the effects of
trans
-fatty acids (2 % of total energy, TFA diet) on the loss of strength and aerobic exercise capacity (
V
O
2
peak) with age. SAMP8 mice were studied at two ages (young, 25 weeks; old, 60 weeks) and on two diets (control vs TFA). Body composition, grip strength,
V
O
2
peak, blood metabolites, and biochemical parameters were assessed. Body weight, fat mass, and body fat percentage all increased with age (
p
< 0.05) but were not significantly impacted by diet. There was a significant age-related decline in total grip strength as well as that normalized to fat-free mass (FFM) (
p
< 0.05) with a further decrease at old age in these metrics of strength on the TFA diet vs control diet (
p
< 0.05). Total
V
O
2
peak exhibited no change with age or diet, but when normalized to FFM,
V
O
2
peak exhibited age and TFA-related declines (
p
< 0.05). Intramuscular triacylglycerol (
p
< 0.05) and collagen content (
p
< 0.05) significantly increased with age, while blood triacylglycerol was increased by the TFA diet (
p
< 0.05). These data further characterize the SAMP8 mouse as a model for sarcopenia and indicate that dietary fatty acid composition can impact the degree of this age-related loss of physical function.
The accumulation of old and damaged proteins likely contributes to complications of diabetes, but currently no methodology is available to measure the relative age of a specific protein alongside ...assessment of posttranslational modifications (PTM). To accomplish our goal of studying the impact of insulin deficiency and hyperglycemia in type 1 diabetes upon accumulation of old damaged isoforms of plasma apolipoprotein A-1 (ApoA-1), we sought to develop a novel methodology, which is reported here and can also be applied to other specific proteins.
To label newly synthesized proteins, ring-(13)C(6)phenylalanine was intravenously infused for 8 h in type 1 diabetic participants (n = 7) during both insulin treatment and 8 h of insulin deprivation and in nondiabetic participants (n = 7). ApoA-1 isoforms were purified by two-dimensional gel electrophoresis (2DGE) and assessment of protein identity, PTM, and ring-(13)C(6)phenylalanine isotopic enrichment (IE) was performed by tandem mass spectrometry.
Five isoforms of plasma ApoA-1 were identified by 2DGE including ApoA-1 precursor (pro-ApoA-1) that contained the relatively highest IE, whereas the older forms contained higher degrees of damage (carbonylation, deamidation) and far less IE. In type 1 diabetes, the relative ratio of IE of ring-(13)C(6)phenylalanine in an older isoform versus pro-ApoA-1 was higher during insulin deprivation, indicating that de novo synthesized pro-ApoA-1 more rapidly accumulated damage, converting to mature ApoA-1.
We developed a mass spectrometry-based methodology to identify the relative age of protein isoforms. The results demonstrated accelerated oxidative damage to plasma ApoA-1, thus offering a potential mechanism underlying the impact of poor glycemic control in type 1 diabetic patients that affects a patient's risk for vascular disease.
Duchenne muscular dystrophy (DMD) is a severe muscle disease that affects afflicted males from a young age, and the mdx mouse is an animal model of this disease. Although new drugs are in ...development, it is also essential to assess potential dietary therapies that could assist in the management of DMD. In the present study, we compared two diets, high-MUFA diet v. high-PUFA diet, in mdx mice. To generate the high-PUFA diet, a portion of dietary MUFA (oleic acid) was replaced with the dietary essential n-3 PUFA α-linolenic acid (ALA). We sought to determine whether ALA, compared with oleic acid, was beneficial in mdx mice. Consumption of the high-PUFA diet resulted in significantly higher n-3 PUFA content and reduced arachidonic acid content in skeletal muscle phospholipids (PL), while the high-MUFA diet led to higher oleate content in PL. Mdx mice on the high-MUFA diet exhibited 2-fold lower serum creatine kinase activity than those on the high-PUFA diet (P< 0·05) as well as a lower body fat percentage (P< 0·05), but no significant difference in skeletal muscle histopathology results. There was no significant difference between the dietary groups with regard to phosphorylated p65 (an inflammatory marker) in skeletal muscle. In conclusion, alteration of PL fatty acid (FA) composition by the high-PUFA diet made mdx muscle more susceptible to sarcolemmal leakiness, while the high-MUFA diet exhibited a more favourable impact. These results may be important for designing dietary treatments for DMD patients, and future work on dietary FA profiles, such as comparing other FA classes and dose effects, is needed.
•Albumin and hemopexin impair heme-mediated TNF secretion through ROS blockade.•Albumin does not interfere with TLR4 signaling induced by heme.•Albumin and hemopexin enable Heme-LPS synergism through ...ROS and cell death regulation.
Free heme released from hemoglobin contributes to exacerbated inflammation and tissue damage in hemolytic diseases. While a moderate level of free heme does not cause intravascular inflammation by itself, its presence during infection greatly enhances inflammation. Although specific serum proteins have been found to affect heme-induced inflammation, the selective contribution of serum proteins inhibiting macrophage activation by heme or, conversely, amplifying the production of cytokines by macrophages stimulated with heme and microbial molecules, is poorly defined. Here we identified a serum fraction containing proteins with >50 KDa which was capable of inhibiting heme-stimulated TNF production and capable of enabling TNF production under conditions of a heme-LPS synergy. The inhibition of heme-induced TNF production was mimicked by Hemopexin (Hx), human serum albumin (HSA), serum from Hx-knockout mice, and less efficiently by serum from albumin-knockout mice, but not by serum LDL. Hx and HSA inhibited heme-induced ROS generation, MAPK/ Syk phosphorylation and cell death. However, Hx and HSA each also promoted the synergistic relationship between heme and LPS upon TNF production. Serum from Hx-knockout mice was fully capable of enabling this synergy, while serum from albumin-knockout mice was less efficient to promote TNF production under these conditions. Low concentrations of HSA mimicked the ability of serum to enable heme-stimulated IL-1β production after LPS priming, while high concentrations inhibited it. Together, our findings indicate how heme inflammatory effects are restrained in the blood upon sterile hemolysis, yet exacerbate inflammation in the presence of microbes. Moreover, it is interesting to note that opposing effects of serum proteins on heme-induced macrophage activation were selected through evolution, with both effects exerted by Hx and albumin.
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Previously, following derivatization to their 2-nitrophenylhydrazide (2-NPH) derivatives, fatty acid (FA) abundances have been evaluated using high-performance liquid chromatography (HPLC). Although ...the method was sensitive, resolution was insufficient for many of the biologically important FAs. We have developed an enhanced separation of 24 FAs by use of different column temperature, stationary phase, and mobile phase gradient conditions. We applied this method to analysis of mouse skeletal muscle phospholipid and triglyceride. This further development of the chromatographic separation of 2-NPH FAs may lead to greater utility of this HPLC approach.
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