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      Whole-Body Vibration Mimics the Metabolic Effects of Exercise in Male Leptin Receptor–Deficient Mice

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          Abstract

          Whole-body vibration (WBV) has gained attention as a potential exercise mimetic, but direct comparisons with the metabolic effects of exercise are scarce. To determine whether WBV recapitulates the metabolic and osteogenic effects of physical activity, we exposed male wild-type (WT) and leptin receptor–deficient (db/db) mice to daily treadmill exercise (TE) or WBV for 3 months. Body weights were analyzed and compared with WT and db/db mice that remained sedentary. Glucose and insulin tolerance testing revealed comparable attenuation of hyperglycemia and insulin resistance in db/db mice following TE or WBV. Both interventions reduced body weight in db/db mice and normalized muscle fiber diameter. TE or WBV also attenuated adipocyte hypertrophy in visceral adipose tissue and reduced hepatic lipid content in db/db mice. Although the effects of leptin receptor deficiency on cortical bone structure were not eliminated by either intervention, exercise and WBV increased circulating levels of osteocalcin in db/db mice. In the context of increased serum osteocalcin, the modest effects of TE and WBV on bone geometry, mineralization, and biomechanics may reflect subtle increases in osteoblast activity in multiple areas of the skeleton. Taken together, these observations indicate that WBV recapitulates the effects of exercise on metabolism in type 2 diabetes.

          Abstract

          We compared the effects of exercise and whole-body vibration in obese and nonobese mice. The results indicate that whole-body vibration mimics the effects of exercise on metabolism in obese mice.

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          Most cited references49

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          Muscles, exercise and obesity: skeletal muscle as a secretory organ.

          During the past decade, skeletal muscle has been identified as a secretory organ. Accordingly, we have suggested that cytokines and other peptides that are produced, expressed and released by muscle fibres and exert either autocrine, paracrine or endocrine effects should be classified as myokines. The finding that the muscle secretome consists of several hundred secreted peptides provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs, such as adipose tissue, liver, pancreas, bones and brain. However, some myokines exert their effects within the muscle itself. Thus, myostatin, LIF, IL-6 and IL-7 are involved in muscle hypertrophy and myogenesis, whereas BDNF and IL-6 are involved in AMPK-mediated fat oxidation. IL-6 also appears to have systemic effects on the liver, adipose tissue and the immune system, and mediates crosstalk between intestinal L cells and pancreatic islets. Other myokines include the osteogenic factors IGF-1 and FGF-2; FSTL-1, which improves the endothelial function of the vascular system; and the PGC-1α-dependent myokine irisin, which drives brown-fat-like development. Studies in the past few years suggest the existence of yet unidentified factors, secreted from muscle cells, which may influence cancer cell growth and pancreas function. Many proteins produced by skeletal muscle are dependent upon contraction; therefore, physical inactivity probably leads to an altered myokine response, which could provide a potential mechanism for the association between sedentary behaviour and many chronic diseases.
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            Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice.

            The osteoblast-specific secreted molecule osteocalcin behaves as a hormone regulating glucose metabolism and fat mass in two mutant mouse strains. Here, we ask two questions: is the action of osteocalcin on beta cells and adipocytes elicited by the same concentrations of the molecule, and more importantly, does osteocalcin regulate energy metabolism in WT mice? Cell-based assays using isolated pancreatic islets, a beta cell line, and primary adipocytes showed that picomolar amounts of osteocalcin are sufficient to regulate the expression of the insulin genes and beta cell proliferation markers, whereas nanomolar amounts affect adiponectin and Pgc1alpha expression in white and brown adipocytes, respectively. In vivo the same difference exists in osteocalcin's ability to regulate glucose metabolism on the one hand and affect insulin sensitivity and fat mass on the other hand. Furthermore, we show that long-term treatment of WT mice with osteocalcin can significantly weaken the deleterious effect on body mass and glucose metabolism of gold thioglucose-induced hyperphagia and high-fat diet. These results establish in WT mice the importance of this novel molecular player in the regulation of glucose metabolism and fat mass and suggest that osteocalcin may be of value in the treatment of metabolic diseases.
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              SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene.

              Sterol regulatory element 1 (SRE-1), a decamer (5'-ATC-ACCCCAC-3') flanking the low density lipoprotein (LDL) receptor gene, activates transcription in sterol-depleted cells and is silenced by sterols. We report the cDNA cloning of human SREBP-1, a protein that binds SRE-1, activates transcription, and thereby mediates the final regulatory step in LDL metabolism. SREBP-1 contains a basic-helix-loop-helix-leucine zipper (bHLH-ZIP) motif, but it differs from other bHLH-ZIP proteins in its larger size (1147 amino acids) and target sequence. Instead of an inverted repeat (CANNTG), the target for all known bHLH-ZIP proteins, SRE-1 contains a direct repeat of CAC. Overexpression of SREBP-1 activates transcription of reporter genes containing SRE-1 in the absence (15-fold) and presence (90-fold) of sterols, abolishing sterol regulation. We suggest that SREBP-1 is regulated by an unknown factor that is overwhelmed when SREBP-1 is overexpressed. Understanding the regulation of SREBP-1 may be crucial for understanding the control of plasma cholesterol in humans.
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                Author and article information

                Journal
                Endocrinology
                Endocrinology
                endo
                endo
                Endocrinology
                Endocrine Society (Washington, DC )
                0013-7227
                1945-7170
                01 May 2017
                15 March 2017
                : 158
                : 5
                : 1160-1171
                Affiliations
                [1 ]Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia 30912
                [2 ]Department of Orthopedic Surgery, Medical College of Georgia, Augusta University, Augusta, Georgia 30912
                [3 ]Department of Pediatrics, Gastroenterology Division, Medical College of Georgia, Augusta University, Augusta, Georgia 30912
                [4 ]Georgia Prevention Institute, Medical College of Georgia, Augusta University, Augusta, Georgia 30912
                [5 ]Physiology Department, Medical College of Georgia, Augusta University, Augusta, Georgia 30912
                [6 ]Department of Oral Biology, Medical College of Georgia, Augusta University, Augusta, Georgia 30912
                [7 ]Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, Georgia 30912
                [8 ]Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, Maryland 21224
                [9 ]Department of Surgery, Plastic Surgery Division, Medical College of Georgia, Augusta University, Augusta, Georgia 30912
                Author notes
                Address all correspondence and requests for reprints to: Alexis M. Stranahan, PhD, Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, Georgia 30912. E-mail: astranahan@ 123456augusta.edu .
                Article
                endo_161250
                10.1210/en.2016-1250
                5460837
                28323991
                5932d2b4-47e1-460f-ab25-d6485cbd1f4f
                History
                : 20 April 2016
                : 02 February 2017
                Page count
                Figures: 6, Tables: 1, Equations: 0, References: 65, Pages: 12
                Categories
                Special Section: Metabolism in Endocrine Health and Disease
                Research Articles
                Diabetes - Insulin - Glucagon - Gastrointestinal

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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