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Amino Acid Sensing in Muscle: Role of the lysosome and the effect of protein supplementation on improving amino acid sensitivity in aging muscle
No full textProtein ingestion is a well-studied stimulus for increasing skeletal muscle protein synthesis. Only recently has the mechanism for this phenomenon been elucidated at the cellular level. To this point, most of the mechanistic research into this process has been conducted in human embryonic kidney cells. Therefore, it is necessary to determine if this cellular mechanism is conserved in muscle. If so, it may be possible to manipulate this mechanism in order to enhance skeletal muscle protein turnover, that is the balance between protein synthesis and protein breakdown. Potentially a protein supplement that could exploit this mechanism to promote protein anabolism through either increasing protein synthesis or decreasing protein breakdown would result in improved skeletal muscle health. Reduced strength and muscle mass are predictors of early mortality. This highlights the importance of developing more effective methods to increase muscle mass and strength. Reduced muscle mass and weakness increases the risk for falls in older adults. A fall can lead to a loss of independence and placement in a care facility. Excessive muscle wasting and weakness is also considered a key risk factor for survival with cancer and other diseases. A better understanding of the biology of muscle wasting is needed to develop evidence-based rehabilitation protocols for improving muscle function for a variety of clinical conditions associated with muscle loss
Role of β-aminoisobutyric acid in relation to insulin sensitivity and cardiometabolic health in adults with obesity
No full textβ-aminoisobutyric acid (BAIBA) is a myokine that improves insulin sensitivity, raises fat oxidation, favors glucose homeostasis and lowers inflammation to reduce cardiometabolic risk. BAIBA is reported to be lower in people with obesity. However, there is limited data on whether: a) BAIBA differs in people who have pre-diabetes compared with normal glucose tolerance and b) if BAIBA levels improve by a low calorie diet (LCD) versus LCD plus interval exercise (LCD+INT). PURPOSE: To examine BAIBA in relation to insulin sensitivity and cardiometabolic health before and after lifestyle interventions. METHODS: First, we performed a cross-sectional analysis to compare BAIBA between people with normal glucose tolerance (NGT, N=22, 20F; 48.0±2.4y; 36.9±1.2 kg/m2) and pre-diabetes (PD, n=23 (18 F/ 5 M, 54.2 ± 1.6 yrs, 38.4 ± 1.2 kg/m2). This was followed by a prospective analysis of women with obesity being randomized to LCD (n=12; 48.4 ± 2.5y, 37.8 ± 1.5kg/m2) compared with LCD+INT (n=11; 47.6 ± 4.3y, 37.9 ± 2.3kg/m2) for 2 weeks. In both approaches, we determined BAIBA (mass spectroscopy) in fasting blood as well as examined insulin sensitivity (HOMA-IR, Adipose IR, Matsuda index/SIIS), β-cell function (disposition index (DI) corrected to muscle, liver and/or adipose), glucose tolerance (glucose from a 180 min 75g OGTT), and hepatic insulin clearance (HIC), as well as resting energy expenditure (REE), substrate oxidation (RER, CHOox and Fox), and adipokines (adiponectin and leptin). RESULTS: The results for the cross-sectional analysis indicated no difference in BAIBA among NGT and PD (1.41 ± 0.1 vs. 1.24 ± 0.1uM; P=0.23). However, BAIBA correlated with low plasma insulin (r=-0.391, P=0.03) and blood glucose (r=-0.319, P=0.03) at 180 min of the OGTT. However, improved glucose tolerance was mediated though an adiponectin depedent mechanism (B=-8.78, SE=4.82, 95%CI [-18.57, 1.01], β=-0.28, P=0.077]. For the prospective intervention trial, LCD and LCD+INT increased BAIBA (LCD; 1.50 ± 0.2 vs. 0.97 ± 0.1and LCD+INT; 1.26 ± 0.3 vs. 1.85 ± 0.2uM; P=0.007). Interestingly, BAIBA correlated to lower circulating leptin (r=-0.662, P=0.001), body weight (r=-0.669, P<0.001) and β-cell function (DImuscle; r=-0.45, P=0.03) as well as CHOox tAUC120 (r=-0.44, P=0.03) during the OGTT. CONCULSION: Taken together, BAIBA appears to relate to glycemic control, circulating insulin, pancreatic function and substrate oxidation in adults with obesity. Thus, additional work is required to further understand how BAIBA contributes to lower cardiometabolic disease risk.M.S.Includes bibliographical reference
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Human brown fat, adiposity, and cardiometabolic health: New pieces to the puzzle
Full text linkBrown adipose tissue (BAT) is an emerging target against obesity and its related metabolic diseases. Wibmer et al.1 recently reported that human BAT is associated with a healthier fat distribution and improved cardiometabolic health independent of adiposity and fat distribution
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Mechanisms of Blood Flow Restriction Exercise in Skeletal Muscle Adaptations
No full textThe maintenance of skeletal muscle mass is crucial for human health and long term survival. However, the aging process is associated with an involuntary loss of muscle mass and the inability to maximally stimulate muscle growth ultimately leading to sarcopenia. Extensive research has been conducted to determine the precise mechanisms by which nutrients, hormones and exercise regulate cell signaling events that convert the anabolic stimulus to a response that enhances cell size. Unfortunately, the research is incomplete considering the insufficient explanation for the impaired muscle synthetic response associated with aging. Interestingly, a novel style of exercise utilizing low-intensity resistance coupled with local vascular occlusion called “blood flow restriction” (BFR) exercise has emerged as an exercise that stimulates muscle growth and muscle protein synthesis to a similar extent for all adults. Research in the past two decades on BFR exercise has been primarily descriptive whereas a mechanistic explanation is lacking as to how a low intensity resistance stimulus is sufficient to promote an increase
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in muscle mass. Research in this dissertation is focused on investigating potential mechanisms that stimulate a muscle anabolic response following BFR exercise. Immediately following BFR exercise as the restriction cuffs are removed, reactive hyperemia occurs, and the increase in nutritive delivery to the muscle is believed to be one of the driving factors that stimulate muscle protein synthesis. Although, mimicking the effect of reactive hyperemia using a pharmacological vasodilator after low-intensity resistance exercise was insufficient to reproduce a similar increase in muscle protein synthesis or anabolic cell signaling. Moreover, mTORC1 is thought to be necessary and required for all cell growth signals; however, this mechanism has yet to be tested with BFR exercise. Use of the competitive mTORC1 inhibitor, rapamycin, determined that BFR exercise does in fact stimulate muscle protein synthesis through the activation of mTORC1. Lastly, metabolic stress such as the accumulation of lactate and G6P have been shown to play a role in the activation of mTORC1 in all muscle fibers contrary to high-intensity exercise that only stimulates fast twitch muscle fibers. Collectively, these studies further our understanding of the underlying mechanisms of BFR exercise
The role of brown adipose tissue on substrate metabolism and insulin sensitivity in humans
No full textBrown adipose tissue (BAT) is a recently re-discovered tissue in humans. The role of BAT in thermogenesis and metabolic regulation has been established in rodents. However, the physiological and clinical significance of this tissue in humans has not been proven yet. The purpose of these investigations was to explore the role of BAT in whole-body energy homeostasis, glucose and lipids kinetics, insulin sensitivity, and thermoregulation in humans.
To this end, we studied men with (BAT+) or without (BAT-) detectable BAT under prolonged mild cold and thermoneutral conditions using infusion of stable isotopic tracers, hyperinsulinemic-euglycemic clamps, indirect calorimetry, and positron emission tomography-computed tomography. A novel method was established to sample the supraclavicular BAT depot and white adipose tissue biopsies were collected from the subcutaneous abdominal area.
During cold exposure, only BAT+ individuals demonstrated a significant increase in whole-body resting energy expenditure, free fatty acid oxidation, glucose disposal, and insulin sensitivity. BAT+ individuals also exhibited a higher increase in whole-body lipolysis during cold exposure, compared to the BAT- group, while they were protected from the cold-induced decrease in adipose tissue insulin sensitivity observed in the BAT- group. With regard to thermoregulation, BAT activity was associated with higher tolerance to cold and change in core body temperature. Functional and molecular analyses of brown and white adipose samples demonstrated the increased thermogenic capacity of BAT mitochondria and the cold-induced up-regulation of genes involved in thermogenesis and lipid metabolism in BAT. The newly established BAT biopsy technique was safe and well tolerated.
These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose and lipid homeostasis, insulin sensitivity, and thermoregulation in humans, and support the notion that human BAT may function as an anti-obesity and anti-diabetic tissue
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