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Biomedical subjects

Frank W Booth

Publications and source records attributed to Frank W Booth.

At least 19 recordsLinked to original sources
PubMed2006

Inactivity induces increases in abdominal fat.

Previously, inducing inactivity for 53 h after 21 days of voluntary running resulted in a 25 and 48% increase in epididymal and omental fat pad weights, respectively, while rats continued to eat more than a group that never had access to a running wheel (J Physiol 565: 911-925, 2005). We wanted to test the hypothesis that inactivity, independent of excessive caloric intake, could induce an increase in fat pad mass. Twenty-one-day-old rats were given access to voluntary running wheels for 42-43 days so that they were running approximately 9 km/day in the last week of running, after which wheels were locked for 5, 53, or 173 h (WL5, WL53, WL173) before the rats were killed. During the 53 and 173 h of inactivity, one group of animals was pair fed (PF) to match sedentary controls, whereas the other continued to eat ad libitum (AL). Epididymal and retroperitoneal fat masses were significantly increased in the WL173-PF vs. the WL5 group, whereas epididymal, perirenal, and retroperitoneal fat masses were all significantly increased in the WL173-AL group compared with the WL5 group. Additionally, hyperplasia, and not hypertrophy, of the epididymal fat mass was responsible for the increase at WL173-AL as demonstrated by a significant increase in cell number vs. WL5, with no change in cell diameter or volume. Thus two important findings have been elucidated: 1) increases in measured abdominal fat masses occur in both AL and PF groups at WL173, and 2) adipocyte expansion via hyperplasia occurred with an ad libitum diet following cessation of voluntary running.

Abdomen↗
PubMed2006

Fundamental questions about genes, inactivity, and chronic diseases.

Currently our society is faced with the challenge of understanding the biological basis for the epidemics of obesity and many chronic diseases, including Type 2 diabetes. Physical inactivity increases the relative risk of coronary artery disease by 45%, stroke by 60%, hypertension by 30%, and osteoporosis by 59%. Moreover, physical inactivity is cited as an actual cause of chronic disease by the US Centers of Disease Control. Physical activity was obligatory for survival for the Homo genus for hundreds of thousands of years. This review will present evidence that suggests that metabolic pathways selected during the evolution of the human genome are inevitably linked to physical activity. Furthermore, as with many other environmental interactions, cycles of physical activity and inactivity interact with genes resulting in a functional outcome appropriate for the environment. However, as humans are less physically active, there is a maladaptive response that leads to metabolic dysfunction and many chronic diseases. How and why these interactions occur are fundamental questions in biology. Finally, a perspective to future research in physical inactivity-gene interaction is presented. This information is necessary to provide the molecular evidence required to further promote the primary prevention of chronic diseases through physical activity, identify those molecules that will allow early disease detection, and provide society with the molecular information needed to counter the current strategy of adding physical inactivity into our lives.

Adaptation, Physiological↗
PubMed2006

Leukemia inhibitory factor restores the hypertrophic response to increased loading in the LIF(-/-) mouse.

Cytokines and growth factors are thought to contribute to skeletal muscle hypertrophy. Leukemia inhibitory factor (LIF), a cytokine, enhances skeletal muscle regeneration; however the role of LIF in skeletal muscle hypertrophy remains uncertain. We examined the hypertrophic ability of the plantaris and soleus muscles in wild-type mice (WT) and LIF knock-out mice [LIF(-/-)] in response to increased mechanical load. Using the functional overload model to induce increases in mechanical load on the plantaris and soleus muscle, WT mice demonstrated increases in plantaris and soleus mass after 7, 21, and 42 days of loading. However, the LIF(-/-) mice had no significant increases in plantaris muscle mass at any time point, while the soleus muscle exhibited a delayed hypertrophic response. Systemic delivery of LIF to the LIF(-/-) mice returned the hypertrophic response to the same levels as the WT mice after 21 days of functional overload. These data demonstrate for the first time that LIF expression in loaded skeletal muscle is critical for the development of skeletal muscle hypertrophy in the functional overload model.

Animals↗
PubMed2006

Neurobiology of exercise.

Voluntary physical activity and exercise training can favorably influence brain plasticity by facilitating neurogenerative, neuroadaptive, and neuroprotective processes. At least some of the processes are mediated by neurotrophic factors. Motor skill training and regular exercise enhance executive functions of cognition and some types of learning, including motor learning in the spinal cord. These adaptations in the central nervous system have implications for the prevention and treatment of obesity, cancer, depression, the decline in cognition associated with aging, and neurological disorders such as Parkinson's disease, Alzheimer's dementia, ischemic stroke, and head and spinal cord injury. Chronic voluntary physical activity also attenuates neural responses to stress in brain circuits responsible for regulating peripheral sympathetic activity, suggesting constraint on sympathetic responses to stress that could plausibly contribute to reductions in clinical disorders such as hypertension, heart failure, oxidative stress, and suppression of immunity. Mechanisms explaining these adaptations are not as yet known, but metabolic and neurochemical pathways among skeletal muscle, the spinal cord, and the brain offer plausible, testable mechanisms that might help explain effects of physical activity and exercise on the central nervous system.

Adaptation, Physiological↗
PubMed2005

Increased mitochondrial glycerol-3-phosphate acyltransferase protein and enzyme activity in rat epididymal fat upon cessation of wheel running.

Triacylglycerol synthesis in rat epididymal fat overshoots sedentary levels at 10, 29, and 53 h of physical inactivity after 21 days of wheel running. The purposes of the present study were to determine 1) whether this effect is also observed after an acute bout of physical activity and 2) what enzymatic changes might contribute to this effect. We show that more than one bout of physical activity, such as that which occurs with 21 days of wheel running, is necessary for palmitic acid incorporation into triacylglyceride (triglyceride synthesis) to overshoot sedentary values, which suggests that pretranslational mechanisms may be responsible for this overshoot effect. Ten hours after 21 days of wheel running, activity of the mitochondrial glycerol-3-phosphate acyltransferase-1 (mtGPAT1) isoform, a key regulator of triacylglycerol synthesis, overshot sedentary values by 48% and remained higher than sedentary values at 29 and 53 h of reduced physical activity. The overshoot in mtGPAT1 activity was accompanied by an increase in mtGPAT protein level. Cyclic AMP response element-binding protein-binding protein level was higher in sedentary 29 h after 21 days of wheel running. AMP kinase-alpha Thr(172) phosphorylation was increased immediately after treadmill running, but decreased to sedentary values by 5 h after activity. Casein kinase-2alpha protein level and activity were unchanged. We conclude that an increase in mtGPAT protein might contribute to the overshoot in triacylglycerol synthesis.

Adenylate Kinase↗
PubMed2005

Age-associated decrease in muscle precursor cell differentiation.

Muscle precursor cells (MPCs) are required for the regrowth, regeneration, and/or hypertrophy of skeletal muscle, which are deficient in sarcopenia. In the present investigation, we have addressed the issue of age-associated changes in MPC differentiation. MPCs, including satellite cells, were isolated from both young and old rat skeletal muscle with a high degree of myogenic purity (>90% MyoD and desmin positive). MPCs isolated from skeletal muscle of 32-mo-old rats exhibited decreased differentiation into myotubes and demonstrated decreased myosin heavy chain (MHC) and muscle creatine kinase (CK-M) expression compared with MPCs isolated from 3-mo-old rats. p27(Kip1) is a cyclin-dependent kinase inhibitor that has been shown to enhance muscle differentiation in culture. Herein we describe our finding that p27(Kip1) protein was lower in differentiating MPCs from skeletal muscle of 32-mo-old rats than in 3-mo-old rat skeletal muscle. Although MHC and CK-M expression were approximately 50% lower in differentiating MPCs isolated from 32-mo-old rats, MyoD protein content was not different and myogenin protein concentration was twofold higher. These data suggest that there are inherent differences in cell signaling during the transition from cell cycle arrest to the formation of myotubes in MPCs isolated from sarcopenic muscle. Furthermore, there is an age-associated decrease in muscle-specific protein expression in differentiating MPCs despite normal MyoD and elevated myogenin levels.

Aging↗
PubMed2005

Sustained rise in triacylglycerol synthesis and increased epididymal fat mass when rats cease voluntary wheel running.

Four-week-old, Fischer-Brown Norway F1-generation male rats were given access to voluntary running wheels for 21 days, and then the wheels were locked for 5 (WL5), 10 (WL10), 29 (WL29), or 53 (WL53) hours. Two other groups (SED5 and SED10) had no access to voluntary running wheels and were killed at the same time as WL5 and WL10, respectively. Absolute and relative epididymal fat mass, mean cell volume, and amount of lipid per cell increased in WL53 relative to all other groups, with no change in cell number. C/EBPalpha protein levels in epididymal fat were 30% greater in SED5 than in WL5. The rate of triacylglycerol synthesis in epididymal fat was 4.2-fold greater in SED5 than in WL5, increased 14-fold between WLS and WL10, and was 79% lower in SED10 than in WL10. Triacylglycerol synthesis remained at this elevated level (at least 3.5-fold greater than SED5) through WL53. Thus, the rapid increase in epididymal fat mass with the cessation of voluntary wheel running is associated with a prolonged overshoot in epididymal fat triacylglycerol synthesis. Moreover, rats without running wheels had a 9.4% lower body mass after 21 days than those with running wheels. The individual mass of seven different muscles from the hindlimb, upper forelimb, and back were each lower in animals without running wheels, suggesting that physical activity in rapidly growing rats may be requisite for optimal muscle development.

Adipose Tissue↗
PubMed2004

Alterations in insulin receptor signalling in the rat epitrochlearis muscle upon cessation of voluntary exercise.

The major purpose of this study was to elucidate mechanisms by which decreasing enhanced physical activity induces decreased insulin sensitivity in skeletal muscle. Rats with access to voluntary running wheels for 3 weeks had their wheels locked for 5 h (WL5), 29 h (WL29), or 53 h (WL53); a separate group of rats never had wheel access (sedentary, SED). Relative to WL5, submaximal insulin-stimulated 2-deoxyglucose uptake into the epitrochlearis muscle was lower in WL53 and SED. Insulin binding, insulin receptor beta-subunit (IRbeta) protein level, submaximal insulin-stimulated IRbeta tyrosine phosphorylation, and glucose transporter-4 protein level were each lower in both WL53 and SED than in WL5 and WL29. Akt/protein kinase B Ser(473) phosphorylation was lower in WL53 and SED than in WL5. Protein levels of protein tyrosine phosphatase-1B, Src homology phosphatase-2, and protein kinase C- did not vary among groups. The amount of protein tyrosine phosphatase-1B, Src homology phosphatase-2, and protein kinase C- associated with IRbeta in insulin-stimulated muscle also did not differ among the four groups. The mean of SED and WL53 had a significantly higher IRbeta-associated protein tyrosine phosphatase-1B than the mean of WL5 and WL29. The enclosure of multiple changes (decreases in insulin binding, IRbeta protein, IRbeta tyrosine phosphorylation, and glucose transporter-4 protein) in the epitrochlearis muscle within the 29th to 53rd hour after cessation of voluntary wheel running raises the possibility that a single regulatory event could be responsible for the coordinated decrease.

Adaptation, Physiological↗
PubMed2004

Increased nuclear proteins in muscle satellite cells in aged animals as compared to young growing animals.

Evidence implies that satellite cells could play some limiting role in aged muscle undergoing repair or maintenance of mass, which is of potential clinical concern as this could contribute to sarcopenia. Further, insufficient information is available concerning the cellular mechanisms responsible for the lower rat satellite cell proliferation in old animals. Thus, it was hypothesized that the following proteins would be increased in nuclei of satellite cells from old rat skeletal muscle: the cyclin-dependent kinase (CDK) inhibitors p21(WAF1/CIP1) and p27(Kip1) as well as the transcription factors p53 and Forkhead box, subgroup O1 (FOXO1). In addition, the NAD(+)-dependent histone deacetylase SIRT1, the mammalian ortholog of the yeast SIR2 (silence information regulator 2) and a member of the Sirtuin family, was hypothesized to decrease in satellite cell nuclei of old rats. Old satellite cells (30-months old) exhibited a lesser number of BrdU-positive cells as compared to satellite cells (3-months old) from young growing animals. Western blot analysis demonstrated that nuclei of old satellite cells accumulated the cell cycle inhibitors p21(WAF1/CIP1) and p27(Kip1). In addition, nuclear p53 and FOXO1 proteins were also higher in old satellite cells than in cells from young growing animals. These data indicated both p53/p21(WAF1/CIP1)- and FOXO1/p27(Kip1)-dependent pathways might contribute to the age-associated decrease in satellite cell proliferation. Cytoplasmic manganese superoxide dismutase (MnSOD), a gene driven by FOXO1, was higher in old satellite cells. Unexpectedly, nuclear SIRT1 was also increased in old satellite cells compared with satellite cells from young growing animals. The physiological significance of enhanced nuclear SIRT1 expression in old satellite cells remains elusive at this time. In summary, satellite cells in old rats have nuclear accumulation of proteins inhibiting the cell cycle as compared to young, growing animals.

Aging↗
PubMed2004

The biochemical basis of the health effects of exercise: an integrative view.

Physical inactivity-gene interactions result in changes in gene expression, leading to phenotypic changes in the skeletal muscle cell. A subpopulation of those genes that show changes in expression during physical inactivity are candidates for the environment-gene interactions that cross a threshold of biological significance such that overt clinical disease occurs. AMP kinase, GLUT4 and myosin heavy chain IIx are proposed as candidates for physical inactivity-modulated genes that have an altered function that may trigger a crossing of a threshold to disease. Future experiments will be needed to test the validity of the ideas presented.

Adenylate Kinase↗
PubMed2004

Insulin-like growth factor 1 and muscle growth: implication for satellite cell proliferation.

Insulin-like growth factor 1 (IGF-1) has been shown to rescue the aging-related or inactivity-induced loss of muscle mass through the activation of satellite cells. However, the signalling pathways and the mechanism by which IGF-1 affects satellite cells have not been not completely identified. The purpose of the present review is to provide current understanding of the cellular and molecular events underlying IGF-1 induced proliferation of satellite cells.

Aging↗
PubMed2004

Sedentary death syndrome.

Sedentary death syndrome (SeDS) is a major public health burden due to its causing multiple chronic diseases and millions of premature deaths each year. Despite the impact of physical inactivity, very little is known about the actual causes of physical inactivity-induced chronic diseases. It is important to study the mechanisms underlying molecular changes related to physical inactivity in order to better understand the scientific basis of individualized exercise prescription and therapies for chronic diseases, and to support improved public health efforts by providing molecular proof that physical inactivity is an actual cause of chronic diseases. Physical activity has a genetic basis. A subpopulation of genes, which have functioned to support physical activity for survival through most of humankind's existence, require daily exercise to maintain long-term health and vitality. Type 2 diabetes (T2D) is an example of a SeDS condition, as it is almost entirely preventable with physical activity. To determine the true role of physical inactivity in the development and progression of T2D, information is presented which indicates that comparisons should be made to physically active controls, rather than sedentary controls, as this population is the healthiest. Use of sedentary subjects as the control group has led to potentially misleading interpretations. If physically active individuals were designated as the control group, a different interpretation would have been drawn. It is thought that there is no difference in GLUT4 concentration between T2D and sedentary groups. However, GLUT4 expression is higher in active controls than in sedentary and T2D groups. Therefore, to obtain causal mechanisms for SeDS in order to allow for scientifically based prevention and therapy strategies, physically active subjects must serve as the control group.

Cause of Death↗
PubMed2004

Control of the size of the human muscle mass.

This review is divided into two parts, the first dealing with the cell and molecular biology of muscle in terms of growth and wasting and the second being an account of current knowledge of physiological mechanisms involved in the alteration of size of the human muscle mass. Wherever possible, attempts have been made to interrelate the information in each part and to provide the most likely explanation for phenomena that are currently only partially understood. The review should be of interest to cell and molecular biologists who know little of human muscle physiology and to physicians, physiotherapists, and kinesiologists who may be familiar with the gross behavior of human muscle but wish to understand more about the underlying mechanisms of change.

Adaptation, Physiological↗
PubMed2004

Eating, exercise, and "thrifty" genotypes: connecting the dots toward an evolutionary understanding of modern chronic diseases.

Survival of Homo sapiens during evolution was dependent on the procurement of food, which in turn was dependent on physical activity. However, food supply was never consistent. Thus it is contended that the ancient hunter-gatherer had cycles of feast and famine, punctuated with obligate periods of physical activity and rest. Hence, gene selection in the Late-Paleolithic era was probably influenced by physical activity and rest. To ensure survival during periods of famine, certain genes evolved to regulate efficient intake and utilization of fuel stores. Such genes were termed "thrifty genes" in 1962. Furthermore, convincing evidence shows that this ancient genome has remained essentially unchanged over the past 10,000 years and certainly not changed in the past 40-100 years. Although the absolute caloric intake of modern-day humans is likely lower compared with our hunter-gatherer ancestors, it is nevertheless in positive caloric balance in the majority of the US adult population mainly due to the increased sedentary lifestyle in present society. We contend that the combination of continuous food abundance and physical inactivity eliminates the evolutionarily programmed biochemical cycles emanating from feast-famine and physical activity-rest cycles, which in turn abrogates the cycling of certain metabolic processes, ultimately resulting in metabolic derangements such as obesity and Type 2 diabetes. In this context, we postulate that perhaps a crucial mechanism to break the stall of the metabolic processes would be via exercise through the regulation of "physical activity genes," some of which may also be potential candidates for the "thrifty genes" of our hunter-gatherer ancestors. Therefore, the identification of such "thrifty gene" candidates would help provide insight into the pathogenetic processes of the numerous physical inactivity-mediated disorders.

Biological Evolution↗
PubMed2004

Regrowth of skeletal muscle atrophied from inactivity.

The current state of knowledge regarding regrowth of skeletal muscle after inactivity-induced atrophy is reviewed. Muscle regrowth is incomplete after hindlimb suspension in juvenile rats and after limb immobilization in old animals. The process of regrowth from immobilization-induced atrophy likely involves the reversal of directional changes in molecules producing muscle loss while initiating anabolic processes for regrowth of muscle mass. Unfortunately, the molecular mechanisms responsible for successful, or failed, muscle regrowth are not well understood. The purpose of the review is to provide current knowledge about the biology of muscle regrowth from inactivity-induced atrophy.

Age Factors↗