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      Brown adipose tissue but not tibia exhibits a dramatic response to acute reduction in environmental temperature in growing male mice

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          Abstract

          Mice are typically housed at room temperature (∼22 °C), which is well below their thermoneutral zone and results in cold stress. Chronic cold stress leads to increased adaptive thermogenesis and reductions in cancellous bone volume and bone marrow adipose tissue mass in long bones of growing mice. There is strong evidence that increased neuronal activity initiates the metabolic response of intrascapular brown adipose tissue (BAT) to cold stress, but it is less clear whether bone is regulated through a similar mechanism. Therefore, we compared the short-term response of BAT and whole tibia to a reduction in environmental temperature. To accomplish this, we transferred a group of 6-week-old male mice from 32 °C to 22 °C housing and sacrificed the mice 24 h later. Age-matched controls were maintained at 32 °C. We then evaluated expression levels of a panel of genes related to adipocyte differentiation and fat metabolism in BAT and tibia, and a panel of genes related to bone metabolism in tibia. The decrease in housing temperature resulted in changes in expression levels for 47/86 genes related to adipocyte differentiation and fat metabolism in BAT, including 9-fold and 17-fold increases in Ucp1 and Dio2, respectively. In contrast, only 1/86 genes related to adipocyte differentiation and fat metabolism and 4/84 genes related to bone metabolism were differentially expressed in tibia. These findings suggest that bone, although innervated with sensory and sympathetic neurons, does not respond as rapidly as BAT to changes in environmental temperature.

          Highlights

          • Mice are typically housed at ∼22 °C, a temperature below thermoneutral (∼32 °C).

          • We compared 24-hr response of BAT and tibia to a reduction in temperature.

          • Decreased temperature resulted in changes in expression for 48/86 genes in BAT.

          • Only 1/86 genes were differentially expressed in tibia.

          • Bone does not respond as rapidly as BAT to changes in environmental temperature.

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          Most cited references41

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          Brown adipose tissue: function and physiological significance.

          The function of brown adipose tissue is to transfer energy from food into heat; physiologically, both the heat produced and the resulting decrease in metabolic efficiency can be of significance. Both the acute activity of the tissue, i.e., the heat production, and the recruitment process in the tissue (that results in a higher thermogenic capacity) are under the control of norepinephrine released from sympathetic nerves. In thermoregulatory thermogenesis, brown adipose tissue is essential for classical nonshivering thermogenesis (this phenomenon does not exist in the absence of functional brown adipose tissue), as well as for the cold acclimation-recruited norepinephrine-induced thermogenesis. Heat production from brown adipose tissue is activated whenever the organism is in need of extra heat, e.g., postnatally, during entry into a febrile state, and during arousal from hibernation, and the rate of thermogenesis is centrally controlled via a pathway initiated in the hypothalamus. Feeding as such also results in activation of brown adipose tissue; a series of diets, apparently all characterized by being low in protein, result in a leptin-dependent recruitment of the tissue; this metaboloregulatory thermogenesis is also under hypothalamic control. When the tissue is active, high amounts of lipids and glucose are combusted in the tissue. The development of brown adipose tissue with its characteristic protein, uncoupling protein-1 (UCP1), was probably determinative for the evolutionary success of mammals, as its thermogenesis enhances neonatal survival and allows for active life even in cold surroundings.
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            Towards a molecular understanding of adaptive thermogenesis.

            Obesity results when energy intake exceeds energy expenditure. Naturally occurring genetic mutations, as well as ablative lesions, have shown that the brain regulates both aspects of energy balance and that abnormalities in energy expenditure contribute to the development of obesity. Energy can be expended by performing work or producing heat (thermogenesis). Adaptive thermogenesis, or the regulated production of heat, is influenced by environmental temperature and diet. Mitochondria, the organelles that convert food to carbon dioxide, water and ATP, are fundamental in mediating effects on energy dissipation. Recently, there have been significant advances in understanding the molecular regulation of energy expenditure in mitochondria and the mechanisms of transcriptional control of mitochondrial genes. Here we explore these developments in relation to classical physiological views of adaptive thermogenesis.
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              The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue

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                Author and article information

                Contributors
                Journal
                Bone Rep
                Bone Rep
                Bone Reports
                Elsevier
                2352-1872
                08 August 2023
                December 2023
                08 August 2023
                : 19
                : 101706
                Affiliations
                [a ]Skeletal Biology Laboratory, School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA
                [b ]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, 107B Milam Hall, Oregon State University, Corvallis, OR 97331, USA. russell.turner@ 123456oregonstate.edu
                Article
                S2352-1872(23)00054-2 101706
                10.1016/j.bonr.2023.101706
                10448410
                6dde7ebe-f5c5-46f8-9edc-1f6e62f2dc40
                © 2023 The Authors. Published by Elsevier Inc.

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

                History
                : 1 July 2023
                : 4 August 2023
                : 7 August 2023
                Categories
                Full Length Article

                mouse,cold stress,adipocyte gene expression,bone,brown adipose tissue

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