transforming-growth-factor-alpha and Weight-Loss

Although there is substantial interest in intermittent fasting as a dietary approach in active individuals, information regarding its effects in elite endurance athletes is currently unavailable. The present parallel randomized trial investigated the effects of a particular intermittent fasting approach, called time-restricted eating (TRE), during 4 weeks of high-level endurance training.. Sixteen elite under-23 cyclists were randomly assigned either to a TRE group or a control group (ND). The TRE group consumed 100% of its estimated daily energy needs in an 8-h time window (from 10:00 a.m. to 6:00 p.m.) whilst energy intake in the ND group was distributed in 3 meals consumed between 7:00 a.m. and 9:00 p.m. Fat and fat-free mass were estimated by bioelectrical impedance analysis and VO. TRE reduced body weight (- 2%; p = 0.04) and fat mass percentage (- 1.1%; p = 0.01) with no change in fat-free mass. Performance tests showed no significant differences between groups, however the peak power output/body weight ratio (PPO/BW) improved in TRE group due to weight loss (p = 0.02). Free testosterone and IGF-1 decreased significantly (p = 0.01 and p = 0.03 respectively) in TRE group. Leucocyte count decreased in ND group (p = 0.02) whilst the neutrophils-to-lymphocytes ratio (NLR) decreased significantly (p = 0.03) in TRE group.. Our results suggest that a TRE program with an 8-h feeding window elicits weight loss, improves body composition and increases PPO/BW in elite cyclists. TRE could also be beneficial for reducing inflammation and may have a protective effect on some components of the immune system. Overall, TRE could be considered as a component of a periodized nutrition plan in endurance athletes.. This trial was retrospectively registered at clinicaltrials.gov as NCT04320784 on 25 March 2020.

Topics: Athletes; Athletic Performance; Basal Metabolism; Bicycling; Body Composition; Creatinine; Diet; Electric Impedance; Energy Intake; Fasting; Humans; Immune System; Insulin-Like Growth Factor I; Interleukin-6; Leukocyte Count; Lymphocyte Count; Male; Sports Nutritional Physiological Phenomena; Testosterone; Time Factors; Transforming Growth Factor alpha; Weight Loss; Young Adult

The growth factor, transforming growth factor-alpha (TGF-alpha) is strongly expressed in the hypothalamic circadian pacemaker, the suprachiasmatic nucleus (SCN). TGF-alpha is one of several SCN peptides recently suggested to function as a circadian output signal for the regulation of locomotor activity rhythms in nocturnal rodents. When infused in the brain, TGF-alpha suppresses activity. TGF-alpha suppresses other behaviors as well including feeding, resulting in weight loss. Elevated TGF-alpha is correlated with some cancers, and it is possible the TGF-alpha and its receptor, the epidermal growth factor receptor (EGFR), mediate fatigue and weight loss associated with cancer. If true for cancers outside of the brain, then systemic TGF-alpha should also affect behavior. We tested this hypothesis in hamsters with intraperitoneal injections or week-long subcutaneous infusions of TGF-alpha. Both treatments suppressed activity and infusions caused reduced food consumption and weight loss. To identify areas of the brain that might mediate these effects of systemic TGF-alpha, we used immunohistochemistry to localize cells with an activated MAP kinase signaling pathway (phosphorylated ERK1). Cells were activated in two hypothalamic areas, the paraventricular nucleus and a narrow region surrounding the third ventricle. These sites could not only be targets of TGF-alpha produced in the SCN but could also mediate effects of elevated TGF-alpha from tumors both within and outside the central nervous system.

Topics: Animals; Cricetinae; Eating; Extracellular Signal-Regulated MAP Kinases; Hypothalamus; Immunohistochemistry; Infusions, Subcutaneous; Injections, Intraperitoneal; Male; Mesocricetus; Mitogen-Activated Protein Kinase 3; Neurons; Phosphorylation; Signal Transduction; Third Ventricle; Time Factors; Transforming Growth Factor alpha; Weight Loss

Transforming growth factor (TGF)-alpha and its receptor, the epidermal growth factor receptor, are induced after lung injury and are associated with remodeling in chronic pulmonary diseases, such as pulmonary fibrosis and asthma. Expression of TGF-alpha in the lungs of adult mice causes fibrosis, pleural thickening, and pulmonary hypertension, in addition to increased expression of a transcription factor, early growth response-1 (Egr-1). Egr-1 was increased in airway smooth muscle (ASM) and the vascular adventitia in the lungs of mice conditionally expressing TGF-alpha in airway epithelium (Clara cell secretory protein-rtTA(+/-)/[tetO](7)-TGF-alpha(+/-)). The goal of this study was to determine the role of Egr-1 in TGF-alpha-induced lung disease. To accomplish this, TGF-alpha-transgenic mice were crossed to Egr-1 knockout (Egr-1(ko/ko)) mice. The lack of Egr-1 markedly increased the severity of TGF-alpha-induced pulmonary disease, dramatically enhancing airway muscularization, increasing pulmonary fibrosis, and causing greater airway hyperresponsiveness to methacholine. Smooth muscle hyperplasia, not hypertrophy, caused the ASM thickening in the absence of Egr-1. No detectable increases in pulmonary inflammation were found. In addition to the airway remodeling disease, vascular remodeling and pulmonary hypertension were also more severe in Egr-1(ko/ko) mice. Thus, Egr-1 acts to suppress epidermal growth factor receptor-mediated airway and vascular muscularization, fibrosis, and airway hyperresponsiveness in the absence of inflammation. This provides a unique model to study the processes causing pulmonary fibrosis and ASM thickening without the complicating effects of inflammation.

Topics: Airway Resistance; Albuterol; Animals; Bronchial Hyperreactivity; Cells, Cultured; Disease Models, Animal; Early Growth Response Protein 1; ErbB Receptors; Fibroblasts; Humans; Hyperplasia; Lung; Lung Compliance; Methacholine Chloride; Mice; Mice, Knockout; Mice, Transgenic; Muscle, Smooth; Muscle, Smooth, Vascular; Pulmonary Artery; Pulmonary Fibrosis; Recombinant Fusion Proteins; Transforming Growth Factor alpha; Weight Loss

Transforming growth factor-alpha (TGF-alpha) is a candidate output signal of the hypothalamic circadian pacemaker. TGF-alpha is expressed in the suprachiasmatic nucleus (SCN) of rats, hamsters, and rhesus macaques [A. Kramer, F.C. Yang, P. Snodgrass, X. Li, T.E. Scammell, F.C. Davis and C.J. Weitz, Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor signaling, Science, 294 (2001) 2511-5., X. Li, N. Sankrithi and F.C. Davis, Transforming growth factor-alpha is expressed in astrocytes of the suprachiasmatic nucleus in hamster: role of glial cells in circadian clocks, Neuroreport, 13 (2002) 2143-7., Y.J. Ma, M.E. Costa and S.R. Ojeda, Developmental expression of the genes encoding transforming growth factor alpha and its receptor in the hypothalamus of female rhesus macaques, Neuroendocrinology, 60 (1994) 346-59., Y.J. Ma, M.P. Junier, M.E. Costa and S.R. Ojeda, Transforming growth factor-alpha gene expression in the hypothalamus is developmentally regulated and linked to sexual maturation, Neuron, 9 (1992) 657-70.]. TGF-alpha reversibly inhibits wheel-running activity during long-term infusions into the third ventricle of hamsters (2 weeks, intracerebroventricular or ICV) [A. Kramer, F.C. Yang, P. Snodgrass, X. Li, T.E. Scammell, F.C. Davis and C.J. Weitz, Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor signaling, Science, 294 (2001) 2511-5.], and this effect appears to be mediated by the epidermal growth factor receptor (EGFR or ErbB-1) [A. Kramer, F.C. Yang, P. Snodgrass, X. Li, T.E. Scammell, F.C. Davis and C.J. Weitz, Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor signaling, Science, 294 (2001) 2511-5.]. Here, we demonstrate that this inhibitory effect is not restricted to wheel-running behavior or to mediation by the EGFR. Using direct observation, we found the effects of long-term TGF-alpha infusion (ICV, 12 microl/day, 3.3 microM) to be more general than previously reported. Other active behaviors such as grooming and feeding were reversibly inhibited and hamsters showed dramatic weight loss as a result of reduced feeding (34% of body weight over 19 days). TGF-alpha did not disrupt a non-behavioral rhythm, the rhythm in pineal melatonin. Wheel-running activity was also inhibited by another epidermal growth factor-like (EGF-like) peptide, neuregulin (NRG-1), that binds to different ErbB receptors. Like TGF-alpha, NRG-1 caused a significant weight loss. We also show

Topics: Animals; Cricetinae; Eating; ErbB Receptors; Injections, Intraventricular; Intracellular Signaling Peptides and Proteins; Male; Mesocricetus; Motor Activity; Neuregulin-1; Neuropeptides; Orexin Receptors; Orexins; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Transforming Growth Factor alpha; Weight Loss

Pain and cachexia are two of the most debilitating aspects of rheumatoid arthritis. Despite that, the mechanisms by which they are mediated are not well understood. We provide evidence that nerve growth factor (NGF), a secreted regulatory protein that controls neuronal survival during development, is a key mediator of pain and weight loss in auto-immune arthritis. Function blocking antibodies to NGF completely reverse established pain in rats with fully developed arthritis despite continuing joint destruction and inflammation. Likewise, these antibodies reverse weight loss while not having any effect on levels of the pro-cachectic agent tumor necrosis factor (TNF). Taken together, these findings argue that pathological joint pain and joint destruction are mechanistically independent processes and that NGF regulates an alternative cachexia pathway that is independent or downstream of TNF.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Arthritis, Experimental; Cachexia; Dose-Response Relationship, Drug; Escherichia coli Proteins; Humans; Hyperalgesia; Indomethacin; Male; Nerve Growth Factor; Pain Measurement; Rats; Rats, Inbred Lew; Severity of Illness Index; Time Factors; Transforming Growth Factor alpha; Weight Loss

A problem in lung transplantation is tracheal or bronchial dehiscence from ischemia. To determine if an angiogenic factor applied to the airway would improve capillary regrowth, a three-ring segment of trachea was completely severed and sutured in rats. In one group of animals the ischemic segment was wrapped with Gelfoam soaked in an angiogenic factor, transforming growth factor-alpha. In a second group the ischemic area was wrapped with Gelfoam soaked with only the vehicle. In a third group the devascularized area received no additional treatment. One animal from each group was killed daily for 7 days after operation. The tracheal vasculature was cast and viewed by light and scanning electron microscopy. None of the four animals that died early were in the transforming growth factor-alpha group. All animals lost weight between the day of operation and death, but this was least in the transforming growth factor-alpha group (p = 0.05). The light microscopy showed ischemic changes and the development of granulation tissue. The scanning electron microscopy of the vascular casts showed extensive loss of the vessels in the cut area. On day 1 the vessels of all animals dilated and their walls became rough. By day 3 a few corkscrew vessels penetrated the ischemic zone. By day 4 the animal that received transforming growth factor-alpha had more capillaries than the others. By day 6 revascularization in the transforming growth factor-alpha animal was abundant. Besides budding, new capillaries appeared to develop by lateral growth. After the fifth day vessels about 30 to 50 microns in diameter bulged focally. On the bulges, ridges the size, shape, and pattern of capillaries formed. Capillary formation in this manner has not been reported previously. Revascularization emerged sooner and more extensively with transforming growth factor-alpha. No adverse effect of transforming growth factor-alpha was found.

Topics: Animals; Capillaries; Ischemia; Male; Microscopy, Electron, Scanning; Neovascularization, Pathologic; Rats; Rats, Sprague-Dawley; Trachea; Transforming Growth Factor alpha; Weight Loss