Keiichi Watanabe

Bio: Keiichi Watanabe is an academic researcher. The author has contributed to research in topics: Myokine & Internal medicine. The author has an hindex of 2, co-authored 2 publications receiving 109 citations.

Upregulation of circulating IL-15 by treadmill running in healthy individuals: is IL-15 an endocrine mediator of the beneficial effects of endurance exercise?

Abstract: The beneficial effects of endurance exercise include insulin-sensitization and reduction of fat mass Limited knowledge is available about the mechanisms by which endurance exercise exerts the salutary effects Myokines, cytokines secreted by skeletal muscle, have been recognized as a potential mediator Recently, a role of skeletal muscle-derived interleukin-15 (IL-15) in improvement of fat-lean body mass composition and insulin sensitivity has been proposed Yet, previous studies have reported that endurance training does not increase production or secretion of IL-15 in skeletal muscle Here, we show that in opposition to previous findings, 30-min treadmill running at 70% of age-predicted maximum heart rate resulted in a significant increase in circulating IL-15 level in untrained healthy young men These findings suggest that IL-15 might play a role in the systemic anti-obesogenic and insulin-sensitizing effects of endurance exercise, not only as a paracrine and autocrine but also as an endocrine factor

Guanabenz, an antihypertensive centrally acting alpha2-agonist, suppresses morning elevations in aggregation of human platelets.

Abstract: To determine whether the antihypertensive agent guanabenz affects the circadian rhythm in the hemorheologic properties of the platelet, we evaluated the aggregability of platelets collected from 11 healthy subjects in the morning and the evening after the oral administration of this agent, daily for 2 weeks. We analyzed platelet aggregation by the turbidimetric method. In an in vitro study, guanabenz, 10 nM-100 microM, did not affect platelet aggregation, whereas epinephrine induced platelet aggregation at an EC50 of 1.5 microM. The healthy volunteers demonstrated a diurnal variation in platelet aggregability that was high in the morning and low in the evening (66 +/- 10% and 56 +/- 11% respectively, of the percent platelet aggregation induced by epinephrine). The same variation was seen with the platelet aggregation induced by adenosine diphosphate (ADP) (62 +/- 8% [morning] vs. 51 +/- 7% [evening]). After the administration of guanabenz, platelet aggregability was significantly reduced in the morning compared with that before drug administration, when platelet aggregation was induced by epinephrine (49 +/- 9%, p < 0.05) or ADP (48 +/- 7%, p < 0.05), although the plasma levels of catecholamine were unchanged. A suppressive effect of guanabenz on platelet aggregability was observed in the evening, as the platelets were stimulated by epinephrine (38 +/- 9%, p < 0.05), but not by ADP (49 +/- 5%). Findings suggest that guanabenz mainly suppressed the morning enhancement in platelet aggregability, which contributes to the formation of intravascular thrombi. Thus, in addition to its antihypertensive actions, guanabenz may help to reduce the risk of vascular accidents, which frequently occur in the morning.

Administration of Jerusalem artichoke reduces the postprandial plasma glucose and glucose-dependent insulinotropic polypeptide (GIP) concentrations in humans

Abstract: Background The consumption of Jerusalem artichoke has multiple beneficial effects against diabetes and obesity. Objective The aim of this study was to determine the effect of a single administration of Jerusalem artichoke tubers on postprandial glycemia and the concentrations of incretin hormones in humans. Method Grated Jerusalem artichoke was administered prior to a meal (Trial 1; white rice for prediabetic participants, n = 10). Dose-dependent effect of Jerusalem artichoke (Trial 2; white rice for prediabetic participants, n = 4) and effect prior to the fat-rich meal were also investigated (Trial 3; healthy participants, n = 5) in this pilot study. Circulating glucose, insulin, triglyceride, glucagon, active glucagon-like peptide-1 (GLP-1), and active glucose-dependent insulinotropic polypeptide (GIP) concentrations were subsequently measured in all the trials. Results Jerusalem artichoke significantly reduced the glucose and GIP concentrations after the consumption of either meal in Trial 1 and Trial 3, whereas there were no differences in the insulin, glucagon, and active GLP-1 concentrations. Also, there was no significant difference in the triglyceride concentration after the ingestion of the fat-rich meal in Trial 3. The glucose and GIP-lowering effects were dose-dependent, and the consumption of at least 100 g of Jerusalem artichoke was required to have these effects in Trial 2. Conclusion This study demonstrates that a single administration of Jerusalem artichoke tubers reduces postprandial glucose and active GIP concentrations in prediabetic and healthy individuals.

Adipo-Myokines: Two Sides of the Same Coin—Mediators of Inflammation and Mediators of Exercise

Abstract: This review summarizes the current literature regarding the most discussed contraction-regulated moykines like IL-6, IL-15, irisin, BDNF, ANGPTL4, FGF21, myonectin and MCP-1. It is suggested that the term myokine is restricted to proteins secreted from skeletal muscle cells, excluding proteins that are secreted by other cell types in skeletal muscle tissue and excluding proteins which are only described on the mRNA level. Interestingly, many of the contraction-regulated myokines described in the literature are additionally known to be secreted by adipocytes. We termed these proteins adipo-myokines. Within this review, we try to elaborate on the question why pro-inflammatory adipokines on the one hand are upregulated in the obese state, and have beneficial effects after exercise on the other hand. Both, adipokines and myokines do have autocrine effects within their corresponding tissues. In addition, they are involved in an endocrine crosstalk with other tissues. Depending on the extent and the kinetics of adipo-myokines in serum, these molecules seem to have a beneficial or an adverse effect on the target tissue.

AMPK in skeletal muscle function and metabolism.

Abstract: Skeletal muscle possesses a remarkable ability to adapt to various physiologic conditions. AMPK is a sensor of intracellular energy status that maintains energy stores by fine-tuning anabolic and catabolic pathways. AMPK's role as an energy sensor is particularly critical in tissues displaying highly changeable energy turnover. Due to the drastic changes in energy demand that occur between the resting and exercising state, skeletal muscle is one such tissue. Here, we review the complex regulation of AMPK in skeletal muscle and its consequences on metabolism ( e.g., substrate uptake, oxidation, and storage as well as mitochondrial function of skeletal muscle fibers). We focus on the role of AMPK in skeletal muscle during exercise and in exercise recovery. We also address adaptations to exercise training, including skeletal muscle plasticity, highlighting novel concepts and future perspectives that need to be investigated. Furthermore, we discuss the possible role of AMPK as a therapeutic target as well as different AMPK activators and their potential for future drug development.-Kjobsted, R., Hingst, J. R., Fentz, J., Foretz, M., Sanz, M.-N., Pehmoller, C., Shum, M., Marette, A., Mounier, R., Treebak, J. T., Wojtaszewski, J. F. P., Viollet, B., Lantier, L. AMPK in skeletal muscle function and metabolism.

A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise

Abstract: Objective Several epidemiological studies have shown that regular exercise can prevent the onset of colon cancer, although the underlying mechanism is unclear. Myokines are secreted skeletal muscle proteins responsible for some exercise-induced health benefits including metabolic improvement and anti-inflammatory effects in organs. The purpose of this study was to identify new myokines that contribute to the prevention of colon tumorigenesis. Methods To identify novel secreted muscle-derived proteins, DNA microarrays were used to compare the transcriptome of muscle tissue in sedentary and exercised young and old mice. The level of circulating secreted protein acidic and rich in cysteine (SPARC) was measured in mice and humans that performed a single bout of exercise. The effect of SPARC on colon tumorigenesis was examined using SPARC-null mice. The secretion and function of SPARC was examined in culture experiments. Results A single bout of exercise increased the expression and secretion of SPARC in skeletal muscle in both mice and humans. In addition, in an azoxymethane-induced colon cancer mouse model, regular low-intensity exercise significantly reduced the formation of aberrant crypt foci in wild-type mice but not in SPARC-null mice. Furthermore, regular exercise enhanced apoptosis in colon mucosal cells and increased the cleaved forms of caspase-3 and caspase-8 in wild-type mice but not in SPARC-null mice. Culture experiments showed that SPARC secretion from myocytes was induced by cyclic stretch and inhibited proliferation with apoptotic effect of colon cancer cells. Conclusions These findings suggest that exercise stimulates SPARC secretion from muscle tissues and that SPARC inhibits colon tumorigenesis by increasing apoptosis.

Sarcopenia, obesity, and natural killer cell immune senescence in aging: altered cytokine levels as a common mechanism.

Abstract: Human aging is characterized by both physical and physiological frailty. A key feature of frailty, sarcopenia is the age-associated decline in skeletal muscle mass, strength, and endurance that characterize even the healthy elderly. Increases in adiposity, particularly in visceral adipose tissue, are almost universal in aging individuals and can contribute to sarcopenia and insulin resistance by increasing levels of inflammatory cytokines known collectively as adipokines. Aging also is associated with declines in adaptive and innate immunity, known as immune senescence, which are risk factors for cancer and all-cause mortality. The cytokine interleukin-15 (IL-15) is highly expressed in skeletal muscle tissue and declines in aging rodent models. IL-15 inhibits fat deposition and insulin resistance, is anabolic for skeletal muscle in certain situations, and is required for the development and survival of natural killer (NK) lymphocytes. We review the effect that adipokines and myokines have on NK cells, with special emphasis on IL-15. We posit that increased adipokine and decreased IL-15 levels during aging constitute a common mechanism for sarcopenia, obesity, and immune senescence.

Role of Myokines in Regulating Skeletal Muscle Mass and Function.

Abstract: Loss of skeletal muscle mass and strength has recently become a hot research topic with the extension of life span and an increasingly sedentary lifestyle in modern society. Maintenance of skeletal muscle mass is considered an essential determinant of muscle strength and function. Myokines are cytokines synthesized and released by myocytes during muscular contractions. They are implicated in autocrine regulation of metabolism in the muscle as well as in the paracrine/endocrine regulation of other tissues and organs including adipose tissue, the liver, and the brain through their receptors. Till date, secretome analysis of human myocyte culture medium has revealed over 600 myokines. In this review article, we summarize our current knowledge of major identified and characterized myokines focusing on their biological activity and function, particularly in muscle mass and function.