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      Long-duration leptin transgene expression in dorsal vagal complex does not alter bone parameters in female Sprague Dawley rats

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          Abstract

          The hypothalamus and dorsal vagal complex (DVC) are both important for integration of signals that regulate energy balance. Increased leptin transgene expression in either the hypothalamus or DVC of female rats was shown to decrease white adipose tissue and circulating levels of leptin and adiponectin. However, in contrast to hypothalamus, leptin transgene expression in the DVC had no effect on food intake, circulating insulin, ghrelin and glucose, nor on thermogenic energy expenditure. These findings imply different roles for hypothalamus and DVC in leptin signaling. Leptin signaling is required for normal bone accrual and turnover. Leptin transgene expression in the hypothalamus normalized the skeletal phenotype of leptin-deficient ob/ ob mice but had no long-duration (≥10 weeks) effects on the skeleton of leptin-replete rats. The goal of this investigation was to determine the long-duration effects of leptin transgene expression in the DVC on the skeleton of leptin-replete rats. To accomplish this goal, we analyzed bone from three-month-old female rats that were microinjected with recombinant adeno-associated virus encoding either rat leptin (rAAV-Leptin, n = 6) or green fluorescent protein (rAAV-GFP, control, n = 5) gene. Representative bones from the appendicular (femur) and axial (3rd lumbar vertebra) skeleton were evaluated following 10 weeks of treatment. Selectively increasing leptin transgene expression in the DVC had no effect on femur cortical or cancellous bone microarchitecture. Additionally, increasing leptin transgene expression had no effect on vertebral osteoblast-lined or osteoclast-lined bone perimeter or marrow adiposity. Taken together, the findings suggest that activation of leptin receptors in the DVC has minimal specific effects on the skeleton of leptin-replete female rats.

          Highlights

          • Leptin is important for energy balance and bone maturation.

          • The dorsal vagal complex (DVC) plays a role in integrating leptin signaling.

          • Increased leptin gene expression in the DVC had no effect on bone in rats.

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          Most cited references63

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Obesity wars: molecular progress confronts an expanding epidemic.

            The worldwide prevalence of obesity is increasing at an alarming rate, with major adverse consequences for human health. This "obesity epidemic" is paralleled by a rapid and substantive increase in our understanding of molecular pathways and physiologic systems underlying the regulation of energy balance. While efforts to address the environmental factors that are responsible for the recent "epidemic" must continue, new molecular and physiologic insights into this system offer exciting possibilities for future development of successful therapies.
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              Appetite control.

              Our understanding of the physiological systems that regulate food intake and body weight has increased immensely over the past decade. Brain centres, including the hypothalamus, brainstem and reward centres, signal via neuropeptides which regulate energy homeostasis. Insulin and hormones synthesized by adipose tissue reflect the long-term nutritional status of the body and are able to influence these circuits. Circulating gut hormones modulate these pathways acutely and result in appetite stimulation or satiety effects. This review discusses central neuronal networks and peripheral signals which contribute energy homeostasis, and how a loss of the homeostatic process may result in obesity. It also considers future therapeutic targets for the treatment of obesity.
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                Author and article information

                Contributors
                Journal
                Bone Rep
                Bone Rep
                Bone Reports
                Elsevier
                2352-1872
                24 April 2024
                June 2024
                24 April 2024
                : 21
                : 101769
                Affiliations
                [a ]Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA
                [b ]Biostatistics Program, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA
                [c ]Center for Healthy Aging Research, Oregon State University, Corvallis, OR 97331, USA
                Author notes
                [* ]Corresponding author at: Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA. urszula.iwaniec@ 123456oregonstate.edu
                Article
                S2352-1872(24)00036-6 101769
                10.1016/j.bonr.2024.101769
                11067478
                38706522
                1081a772-f72a-4284-85c9-3d974e060bcf
                © 2024 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 17 March 2024
                : 21 April 2024
                : 23 April 2024
                Categories
                Full Length Article

                leptin,dorsal vagal complex,hypothalamus,bone,microcomputed tomography,histomorphometry

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