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      Effect of a GH Secretagogue, Anamorelin, on Serum Irisin and Inflammation Levels in Osteosarcopenic Adults

      brief-report

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          Abstract

          Background

          Data suggest an association between GH secretion and circulating levels of the myokine irisin and inflammatory cytokinesIL-6 and high-sensitivity C-reactive protein (hsCRP). The impact of GH secretagogues on these markers is unknown.

          Objectives

          To determine the effect of treatment with the GH secretagogue anamorelin on 12-month changes in serum irisin, IL-6, and hsCRP levels and to assess whether baseline irisin levels modulate the glycemic response to treatment with anamorelin.

          Methods

          This is an ancillary study in 26 older adults with osteosarcopenia who participated in a 12-month trial examining the effect of anamorelin 100 mg/day vs placebo on musculoskeletal outcomes. Serum irisin, IL-6, and hsCRP were measured at baseline and 12 months.

          Results

          Treatment with anamorelin, compared with placebo, did not significantly alter irisin levels [12-month change = 0.50 ± 1.2 (SD) ng/mL in anamorelin group and −0.08 ± 2.3 ng/mL in placebo; P = .191]. Baseline irisin levels were not significantly correlated with 2-month change in fasting glucose levels in the anamorelin group (r = −0.222, P = .46) or the placebo group (r = 0.30, P = .34); however, the slopes of the 2 regression lines describing the relationship by group tended to differ ( P = .0547). Anamorelin treatment for 12 months had no significant effect on serum IL-6 or hsCRP levels.

          Conclusion

          In this small sample of older adults with osteosarcopenia, treatment with the GH secretagogue anamorelin did not significantly alter levels of irisin, IL-6, or hsCRP. Higher baseline irisin levels may attenuate the glycemic response to anamorelin treatment; however, a larger study is needed to confirm this possibility.

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          Most cited references21

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          A PGC1α-dependent myokine that drives browning of white fat and thermogenesis

          Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional coactivator PGC1α Here we show that PGC1α expression in muscle stimulates an increase in expression of Fndc5, a membrane protein that is cleaved and secreted as a new hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be a protein therapeutic for human metabolic disease and other disorders that are improved with exercise.
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            Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials.

            Patients with advanced cancer frequently experience anorexia and cachexia, which are associated with reduced food intake, altered body composition, and decreased functionality. We assessed anamorelin, a novel ghrelin-receptor agonist, on cachexia in patients with advanced non-small-cell lung cancer and cachexia.
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              Irisin prevents and restores bone loss and muscle atrophy in hind-limb suspended mice

              We previously showed that Irisin, a myokine released from skeletal muscle after physical exercise, plays a central role in the control of bone mass. Here we report that treatment with recombinant Irisin prevented bone loss in hind-limb suspended mice when administered during suspension (preventive protocol) and induced recovery of bone mass when mice were injected after bone loss due to a suspension period of 4 weeks (curative protocol). MicroCT analysis of femurs showed that r-Irisin preserved both cortical and trabecular bone mineral density, and prevented a dramatic decrease of the trabecular bone volume fraction. Moreover, r-Irisin protected against muscle mass decline in the hind-limb suspended mice, and maintained the fiber cross-sectional area. Notably, the decrease of myosin type II expression in unloaded mice was completely prevented by r-Irisin administration. Our data reveal for the first time that Irisin retrieves disuse‐induced bone loss and muscle atrophy. These findings may lead to development of an Irisin-based therapy for elderly immobile osteoporotic and physically disable patients, and might represent a countermeasure for astronauts subjected to microgravity-induced bone and muscle losses.
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                Author and article information

                Contributors
                Journal
                J Endocr Soc
                J Endocr Soc
                jes
                Journal of the Endocrine Society
                Oxford University Press (US )
                2472-1972
                19 February 2024
                13 February 2024
                13 February 2024
                : 8
                : 4
                : bvae028
                Affiliations
                Bone Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University , Boston, MA 02108, USA
                Bone Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University , Boston, MA 02108, USA
                Bone Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University , Boston, MA 02108, USA
                Bone Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University , Boston, MA 02108, USA
                Endocrine Division, Tufts Medical Center , Boston, MA 02108, USA
                Author notes
                Correspondence: Bess Dawson-Hughes, MD, Bone Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St, Boston, MA 02108, USA ; Email: bess.dawson-hughes@ 123456tufts.edu .
                Author information
                https://orcid.org/0000-0003-3136-0386
                https://orcid.org/0000-0003-0023-3640
                Article
                bvae028
                10.1210/jendso/bvae028
                10887452
                38405219
                c7d64dd9-7539-401c-98ce-82e291061aaf
                © The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 December 2023
                : 08 February 2024
                : 23 February 2024
                Page count
                Pages: 4
                Funding
                Funded by: National Institutes of Health, DOI 10.13039/100000002;
                Funded by: USDA Agricultural Research Service, DOI 10.13039/100007917;
                Funded by: Helsinn Healthcare, DOI 10.13039/100008129;
                Categories
                Brief Report
                AcademicSubjects/MED00250

                irisin,igf-1,il-6,hscrp,osteosarcopenia
                irisin, igf-1, il-6, hscrp, osteosarcopenia

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