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      Lipid remodeling of adipose tissue in metabolic health and disease

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          Abstract

          Adipose tissue is a dynamic and metabolically active organ that plays a crucial role in energy homeostasis and endocrine function. Recent advancements in lipidomics techniques have enabled the study of the complex lipid composition of adipose tissue and its role in metabolic disorders such as obesity, diabetes, and cardiovascular disease. In addition, adipose tissue lipidomics has emerged as a powerful tool for understanding the molecular mechanisms underlying these disorders and identifying bioactive lipid mediators and potential therapeutic targets. This review aims to summarize recent lipidomics studies that investigated the dynamic remodeling of adipose tissue lipids in response to specific physiological changes, pharmacological interventions, and pathological conditions. We discuss the molecular mechanisms of lipid remodeling in adipose tissue and explore the recent identification of bioactive lipid mediators generated in adipose tissue that regulate adipocytes and systemic metabolism. We propose that manipulating lipid-mediator metabolism could serve as a therapeutic approach for preventing or treating obesity-related metabolic diseases.

          Metabolic disorders: lipid dynamics as biomarkers and therapeutic targets

          Large-scale analyses of lipid composition and distribution in body fat (adipose tissue) have the potential to revolutionize the treatment and prevention of metabolic disorders associated with obesity. Yun-Hee Lee from Seoul National University, South Korea, and colleagues review the intricate molecular mechanisms underlying lipid synthesis, breakdown, and redistribution, both in healthy and diseased states. Advances in ‘lipidomics’, the analysis of the complete set of lipids and their reactions, have helped to illuminate the complex interactions between bioactive lipids and lipid-modifying enzymes. Such interactions play a critical roles in insulin sensitivity, energy expenditure, and other metabolic processes. The authors propose that the signaling pathways involved, along with the bioactive lipid mediators themselves, could serve as biomarkers or therapeutic targets for type 2 diabetes, cardiovascular disease, and various obesity-related conditions.

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          Most cited references146

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          Health benefits of physical activity: the evidence.

          The primary purpose of this narrative review was to evaluate the current literature and to provide further insight into the role physical inactivity plays in the development of chronic disease and premature death. We confirm that there is irrefutable evidence of the effectiveness of regular physical activity in the primary and secondary prevention of several chronic diseases (e.g., cardiovascular disease, diabetes, cancer, hypertension, obesity, depression and osteoporosis) and premature death. We also reveal that the current Health Canada physical activity guidelines are sufficient to elicit health benefits, especially in previously sedentary people. There appears to be a linear relation between physical activity and health status, such that a further increase in physical activity and fitness will lead to additional improvements in health status.
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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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              Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human.

              Brown fat generates heat via the mitochondrial uncoupling protein UCP1, defending against hypothermia and obesity. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here, we report the isolation of "beige" cells from murine white fat depots. Beige cells resemble white fat cells in having extremely low basal expression of UCP1, but, like classical brown fat, they respond to cyclic AMP stimulation with high UCP1 expression and respiration rates. Beige cells have a gene expression pattern distinct from either white or brown fat and are preferentially sensitive to the polypeptide hormone irisin. Finally, we provide evidence that previously identified brown fat deposits in adult humans are composed of beige adipocytes. These data provide a foundation for studying this mammalian cell type with therapeutic potential. PAPERCLIP: Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                yunhee.lee@snu.ac.kr
                Journal
                Exp Mol Med
                Exp Mol Med
                Experimental & Molecular Medicine
                Nature Publishing Group UK (London )
                1226-3613
                2092-6413
                1 September 2023
                1 September 2023
                September 2023
                : 55
                : 9
                : 1955-1973
                Affiliations
                [1 ]College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, ( https://ror.org/04h9pn542) Seoul, Republic of Korea
                [2 ]Department of Materials Science and Engineering, Research Institute of Advanced Materials, Institute of Engineering Research, Bio-MAX Institute, Soft Foundry Institute, Seoul National University, ( https://ror.org/04h9pn542) Seoul, Republic of Korea
                [3 ]School of Biological Sciences, Seoul National University, ( https://ror.org/04h9pn542) Seoul, Republic of Korea
                [4 ]College of Pharmacy, Pusan National University, ( https://ror.org/01an57a31) Busan, Republic of Korea
                Author information
                http://orcid.org/0000-0002-3512-4164
                http://orcid.org/0000-0002-0542-4705
                Article
                1071
                10.1038/s12276-023-01071-4
                10545718
                37653032
                8f844bfd-5c8a-48b0-acc9-9d06a0e3a586
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 27 February 2023
                : 30 May 2023
                : 5 June 2023
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100003725, National Research Foundation of Korea (NRF);
                Award ID: NRF-2019R1C1C1002014
                Award ID: NRF-2018R1A5A2024425
                Award ID: 2022R1A6A3A13071509
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100002551, Seoul National University;
                Award ID: 370C-20210102
                Award Recipient :
                Categories
                Review Article
                Custom metadata
                © Korean Society for Biochemical and Molecular Biology 2023

                Molecular medicine
                obesity,metabolomics
                Molecular medicine
                obesity, metabolomics

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