白色脂肪棕色化的研究进展
Research Progress of the Browning of White Adipose Tissue
摘要: 白色脂肪组织和棕色脂肪组织是哺乳动物体内两种主要的脂肪类型,它们在结构、分布和功能上存在显著差异,对体内能量平衡的调控有着重要的影响。米色脂肪细胞作为介于这两者之间的类型,具有独特的来源和生化特征。近年来,白色脂肪组织的棕色化成为了研究的热点,其在调控体内能量代谢和防治代谢性疾病方面潜在的作用引起了广泛的关注。棕化过程受多种因素的影响,包括运动和饮食、激素、细胞因子、基因调控、肠道微生物、MicroRNA等。激活白色脂肪棕化与代谢改善相关,为糖尿病、肥胖、脂肪肝等代谢相关疾病提供了新的治疗途径和靶点。然而,棕化过程也存在潜在的问题和风险,因为其可能导致脂质代谢紊乱、增加恶病质相关的能量消耗、影响免疫功能、引发炎症反应,甚至对心血管系统造成额外负担。未来的研究应集中在如何优化这一过程,确保转化过程的安全和高效。
Abstract: White adipose tissue (WAT) and brown adipose tissue (BAT) are the two main fat types in mam-mals. They differ significantly in structure, distribution, and function, affecting the energy balance within the human body. Beige (or Brite) adipose tissue, as an intermediate type, has its unique origin and biochemical characteristics. Recently, the browning of white adipose tissue has become a research focus. Its potential in regulating metabolism and preventing diseases has attracted wide-spread interest. This browning process is influenced by various factors, including exercise, diet, hormones, cytokines, genetic regulation, gut microbiota, and MicroRNA, etc. Activation of the browning process correlates with metabolic improvements, offering novel therapeutic strategies and targets for metabolic-related conditions such as diabetes, obesity, fatty liver. However, this process isn’t without risks. It can disrupt lipid metabolism, increase cachexia-related energy con-sumption, impact immunity, trigger inflammation, and potentially burden the cardiovascular sys-tem. Future research should focus on optimizing this process to ensure the safety and efficiency in clinical practice.
文章引用:沈天娇, 杨刚毅. 白色脂肪棕色化的研究进展[J]. 临床医学进展, 2024, 14(2): 2600-2612. https://doi.org/10.12677/ACM.2024.142366

参考文献

[1] Horino, M., Ikeda, K. and Yamada, T. (2022) The Role of Thermogenic Fat Tissue in Energy Consumption. Current Issues in Molecu-lar Biology, 44, 3166-3179. [Google Scholar] [CrossRef] [PubMed]
[2] Santillana, N., Astudillo-Guerrero, C., D’Espessailles, A., et al. (2023) White Adipose Tissue Dysfunction: Pathophysiology and Emergent Measurements. Nutrients, 15, Article No. 1722. [Google Scholar] [CrossRef] [PubMed]
[3] Shamsi, F., Wang, C.H. and Tseng, Y.H. (2021) The Evolving View of Thermogenic Adipocytes—Ontogeny, Niche and Function. Nature Reviews Endocrinology, 17, 726-744. [Google Scholar] [CrossRef] [PubMed]
[4] Harms, M. and Seale, P. (2013) Brown and Beige Fat: Development, Function and Therapeutic Potential. Nature Medicine, 19, 1252-1263. [Google Scholar] [CrossRef] [PubMed]
[5] Lizcano, F. and Vargas, D. (2016) Biology of Beige Adipocyte and Possible Therapy for Type 2 Diabetes and Obesity. Internet Journal of Endocrinology, 2016, Article ID: 9542061. [Google Scholar] [CrossRef] [PubMed]
[6] Klepac, K., Georgiadi, A., Tschop, M., et al. (2019) The Role of Brown and Beige Adipose Tissue in Glycaemic Control. Molecular Aspects of Medicine, 68, 90-100. [Google Scholar] [CrossRef] [PubMed]
[7] Wang, W. and Seale, P. (2016) Control of Brown and Beige Fat Development. Nature Reviews Molecular Cell Biology, 17, 691-702. [Google Scholar] [CrossRef] [PubMed]
[8] Yook, J.S. and Kajimura, S. (2022) Is Thermogenesis Really Needed for Brown Adipose Tissue-Mediated Metabolic Benefit? Journal of Clinical Investigation, 132, e159296. [Google Scholar] [CrossRef
[9] Tran, T.T. and Kahn, C.R. (2010) Transplantation of Adipose Tissue and Stem Cells: Role in Metabolism and Disease. Nature Reviews Endocrinology, 6, 195-213. [Google Scholar] [CrossRef] [PubMed]
[10] Darcy, J., Fang, Y., McFadden, S., et al. (2020) Integrated Metabolomics Reveals Altered Lipid Metabolism in Adipose Tissue in a Model of Extreme Longevity. GeroScience, 42, 1527-1546. [Google Scholar] [CrossRef] [PubMed]
[11] Anantha, P., Liu, Z., Raj, P., et al. (2023) Optical Diffraction Tomography and Raman Spectroscopy Reveal Distinct Cellular Phenotypes during White and Brown Adipocyte Differentiation. Biosensors & Bioelec-tronics, 235, Article ID: 115388. [Google Scholar] [CrossRef] [PubMed]
[12] Sheng, Y., Xia, F., Chen, L., et al. (2021) Differential Responses of White Adipose Tissue and Brown Adipose Tissue to Calorie Restriction during Aging. Journals of Geron-tology, Series A: Biological Sciences and Medical Sciences, 76, 393-399. [Google Scholar] [CrossRef] [PubMed]
[13] Var-gas-Castillo, A., Torres, N. and Tovar, A.R. (2021) Endocrine Regulation of Brown and Beige Adipose Tissue. In: Ulloa-Aguirre, A. and Tao, Y.-X., Eds., Cellular Endocrinology in Health and Disease, Elsevier, Amsterdam, 247-259. [Google Scholar] [CrossRef
[14] Gavalda-Navarro, A., Villarroya, J., Cereijo, R., et al. (2022) The Endocrine Role of Brown Adipose Tissue: An Update on Actors and Actions. Reviews in Endocrine & Metabolic Disorders, 23, 31-41. [Google Scholar] [CrossRef] [PubMed]
[15] Ahmad, B., Vohra, M.S., Saleemi, M.A., et al. (2021) Brown/Beige Adipose Tissues and the Emerging Role of Their Secretory Factors in Improving Metabolic Health: The Batokines. Biochimie, 184, 26-39. [Google Scholar] [CrossRef] [PubMed]
[16] Ziqubu, K., Dludla, P.V., Mabhida, S.E., et al. (2024) Brown Adipose Tis-sue-Derived Metabolites and Their Role in Regulating Metabolism. Metabolism, 150, Article ID: 155709. [Google Scholar] [CrossRef] [PubMed]
[17] Scheja, L. and Heeren, J. (2019) The Endocrine Function of Adipose Tissues in Health and Cardiometabolic Disease. Nature Reviews Endocrinology, 15, 507-524. [Google Scholar] [CrossRef] [PubMed]
[18] Lee, E., Korf, H. and Vidal-Puig, A. (2023) An Adipocentric Perspective on the Development and Progression of Non-Alcoholic Fatty Liver Disease. Journal of Hepatology, 78, 1048-1062. [Google Scholar] [CrossRef] [PubMed]
[19] Xiang, A.S., Meikle, P.J., Carey, A.L., et al. (2018) Brown Adipose Tissue and Lipid Metabolism: New Strategies for Identification of Activators and Biomarkers with Clinical Potential. Pharmacology & Therapeu-tics, 192, 141-149. [Google Scholar] [CrossRef] [PubMed]
[20] Wang, Z., Wang, Q.A., Liu, Y., et al. (2021) Energy Metabolism in Brown Adipose Tissue. FEBS Journal, 288, 3647- 3662. [Google Scholar] [CrossRef] [PubMed]
[21] Ravussin, E. and Galgani, J.E. (2011) The Implication of Brown Adipose Tissue for Humans. Annual Review of Nutrition, 31, 33-47. [Google Scholar] [CrossRef] [PubMed]
[22] Ussar, S., Lee, K.Y., Dankel, S.N., et al. (2014) ASC-1, PAT2, and P2RX5 Are Cell Surface Markers for White, Beige, and Brown Adipocytes. Science Translational Medicine, 6, 247ra103. [Google Scholar] [CrossRef] [PubMed]
[23] Shinoda, K., Luijten, I.H., Hasegawa, Y., et al. (2015) Genetic and Functional Characterization of Clonally Derived Adult Human Brown Adipocytes. Nature Medicine, 21, 389-394. [Google Scholar] [CrossRef] [PubMed]
[24] Li, P., Song, R., Du, Y., et al. (2022) Adtrp Regulates Thermogenic Activity of Adipose Tissue via Mediating the Secretion of S100b. Cellular and Molecular Life Sciences, 79, Article No. 407. [Google Scholar] [CrossRef] [PubMed]
[25] Basse, A.L., Nielsen, K.N., Karavaeva, I., et al. (2023) NAMPT-Dependent NAD(+) Biosynthesis Controls Circadian Metabolism in a Tissue-Specific Manner. Proceedings of the National Academy of Sciences of the United States of America, 120, e2220102120. [Google Scholar] [CrossRef] [PubMed]
[26] Kotenkova, E., Fedulova, L. and Chernukha, I. (2022) White, Beige and Brown Adipose Tissue: Structure, Function, Specific Features and Possibility Formation and Divergence in Pigs. Foods and Raw Materials, 10, 10-18. [Google Scholar] [CrossRef
[27] Shinde, A.B., Song, A. and Wang, Q.A. (2021) Brown Adipose Tissue Heterogeneity, Energy Metabolism, and Beyond. Frontiers in Endocrinology, 12, Article ID: 651763. [Google Scholar] [CrossRef] [PubMed]
[28] Kajimura, S. and Saito, M. (2014) A New Era in Brown Adipose Tissue Biolo-gy: Molecular Control of Brown Fat Development and Energy Homeostasis. Annual Review of Physiology, 76, 225-249. [Google Scholar] [CrossRef] [PubMed]
[29] Altinova, A.E. (2022) Beige Adipocyte as the Flame of White Adipose Tissue: Regulation of Browning and Impact of Obesity. Journal of Clinical Endocrinology & Metabolism, 107, e1778-e1788. [Google Scholar] [CrossRef] [PubMed]
[30] Daquinag, A.C., Gao, Z., Yu, Y., et al. (2022) Endothelial TrkA Coordinates Vas-cularization and Innervation in Thermogenic Adipose Tissue and Can Be Targeted to Control Metabolism. Molecular Metabolism, 63, Article ID: 101544. [Google Scholar] [CrossRef] [PubMed]
[31] Singh, R., Barrios, A., Dirakvand, G., et al. (2021) Hu-man Brown Adipose Tissue and Metabolic Health: Potential for Therapeutic Avenues. Cells, 10, Article No. 3030. [Google Scholar] [CrossRef] [PubMed]
[32] Becher, T., Palanisamy, S., Kramer, D.J., et al. (2021) Brown Adipose Tissue Is Associated with Cardiometabolic Health. Nature Medicine, 27, 58-65. [Google Scholar] [CrossRef] [PubMed]
[33] Carpen-tier, A.C., Blondin, D.P., Haman, F., et al. (2023) Brown Adipose Tissue—A Translational Perspective. Endocrine Reviews, 44, 143-192. [Google Scholar] [CrossRef] [PubMed]
[34] Xu, Z., You, W., Zhou, Y., et al. (2019) Cold-Induced Lipid Dynamics and Transcriptional Programs in White Adipose Tissue. BMC Biology, 17, Article No. 74. [Google Scholar] [CrossRef] [PubMed]
[35] Levy, S.B. and Leonard, W.R. (2022) The Evolutionary Significance of Human Brown Adipose Tissue: Integrating the Timescales of Adaptation. Evolutionary Anthropology, 31, 75-91. [Google Scholar] [CrossRef] [PubMed]
[36] Scheele, C. and Nielsen, S. (2017) Metabolic Regulation and the Anti-Obesity Perspec-tives of Human Brown Fat. Redox Biology, 12, 770-775. [Google Scholar] [CrossRef] [PubMed]
[37] Pilkington, A.C., Paz, H.A. and Wankhade, U.D. (2021) Beige Adipose Tissue Identification and Marker Specificity—Overview. Frontiers in Endocrinology, 12, Article ID: 599134. [Google Scholar] [CrossRef] [PubMed]
[38] Hondares, E., Rosell, M., Diaz-Delfin, J., et al. (2011) Peroxisome Proliferator-Activated Receptor Alpha (PPARalpha) Induces PPARgamma Coactivator 1alpha (PGC-1alpha) Gene Ex-pression and Contributes to Thermogenic Activation of Brown Fat: Involvement of PRDM16. Journal of Biological Chemistry, 286, 43112-43122. [Google Scholar] [CrossRef
[39] Martinez-Tellez, B., Sanchez-Delgado, G., Acosta, F.M., et al. (2022) No Evi-dence of Brown Adipose Tissue Activation after 24 Weeks of Supervised Exercise Training in Young Sedentary Adults in the ACTIBATE Randomized Controlled Trial. Nature Communications, 13, Article No. 5259. [Google Scholar] [CrossRef] [PubMed]
[40] Harb, E., Kheder, O., Poopalasingam, G., et al. (2023) Brown Adipose Tissue and Regulation of Human Body Weight. Diabetes/Metabolism Research and Reviews, 39, e3594. [Google Scholar] [CrossRef] [PubMed]
[41] Peng, W.Q., Xiao, G., Li, B.Y., et al. (2021) l-Theanine Activates the Browning of White Adipose Tissue through the AMPK/alpha-Ketoglutarate/Prdm16 Axis and Ameliorates Diet-Induced Obesity in Mice. Diabetes, 70, 1458-1472. [Google Scholar] [CrossRef] [PubMed]
[42] Osuna-Prieto, F.J., Martinez-Tellez, B., Segura-Carretero, A., et al. (2021) Activation of Brown Adipose Tissue and Promotion of White Adipose Tissue Browning by Plant-Based Dietary Components in Rodents: A Sys-tematic Review. Advances in Nutrition, 12, 2147-2156. [Google Scholar] [CrossRef] [PubMed]
[43] De Carvalho, F.G., Brandao, C.F.C., Batitucci, G., et al. (2021) Taurine Supplementation Associated with Exercise Increases Mitochondrial Activity and Fatty Acid Oxidation Gene Expression in the Subcutaneous White Adipose Tissue of Obese Women. Clinical Nutrition, 40, 2180-2187. [Google Scholar] [CrossRef] [PubMed]
[44] Bao, J.F., She, Q.Y., Hu, P.P., et al. (2022) Irisin, a Fascinating Field in Our Times. Trends in Endocrinology and Metabolism, 33, 601-613. [Google Scholar] [CrossRef] [PubMed]
[45] Homan, E.P., Brandao, B.B., Softic, S., et al. (2021) Differential Roles of FOXO Transcription Factors on Insulin Action in Brown and White Adi-pose Tissue. Journal of Clinical Investigation, 131, e143328. [Google Scholar] [CrossRef
[46] Johann, K., Cremer, A.L., Fischer, A.W., et al. (2019) Thyroid-Hormone-Induced Browning of White Adipose Tissue Does Not Contribute to Thermogenesis and Glucose Consumption. Cell Reports, 27, 3385-3400e3. [Google Scholar] [CrossRef] [PubMed]
[47] Xu, Z., You, W., Liu, J., et al. (2020) Elucidating the Regulatory Role of Mel-atonin in Brown, White, and Beige Adipocytes. Advances in Nutrition, 11, 447-460. [Google Scholar] [CrossRef] [PubMed]
[48] Abu-Odeh, M., Zhang, Y., Reilly, S.M., et al. (2021) FGF21 Promotes Thermo-genic Gene Expression as an Autocrine Factor in Adipocytes. Cell Reports, 35, Article ID: 109331. [Google Scholar] [CrossRef] [PubMed]
[49] Liu, C., Schonke, M., Zhou, E., et al. (2022) Pharmacological Treatment with FGF21 Strongly Improves Plasma Cholesterol Metabolism to Reduce Atherosclerosis. Cardiovascular Research, 118, 489-502. [Google Scholar] [CrossRef] [PubMed]
[50] Choi, Y. and Yu, L. (2021) Natural Bioactive Compounds as Potential Browning Agents in White Adipose Tissue. Pharmaceutical Research, 38, 549-567. [Google Scholar] [CrossRef] [PubMed]
[51] Darcy, J. and Tseng, Y.H. (2019) ComBATing Aging-Does Increased Brown Adipose Tissue Activity Confer Longevity? GeroScience, 41, 285-296. [Google Scholar] [CrossRef] [PubMed]
[52] Um, J.H., Park, S.Y., Hur, J.H., et al. (2022) Bone Morphogenic Protein 9 Is a Novel Thermogenic Hepatokine Secreted in Response to Cold Exposure. Metabolism, Clinical and Experimental, 129, Article ID: 155139. [Google Scholar] [CrossRef] [PubMed]
[53] Maak, S., Norheim, F., Drevon, C.A., et al. (2021) Progress and Challenges in the Biology of FNDC5 and Irisin. Endocrine Reviews, 42, 436-456. [Google Scholar] [CrossRef] [PubMed]
[54] Santos, R.S., Frank, A.P., Fatima, L.A., et al. (2018) Activation of Estrogen Receptor Alpha Induces Beiging of Adipocytes. Molecular Metabolism, 18, 51-59. [Google Scholar] [CrossRef] [PubMed]
[55] Kaikaew, K., Grefhorst, A. and Visser, J.A. (2021) Sex Differ-ences in Brown Adipose Tissue Function: Sex Hormones, Glucocorticoids, and Their Crosstalk. Frontiers in Endocrinology, 12, Arti-cle ID: 652444. [Google Scholar] [CrossRef] [PubMed]
[56] Xue, L., Sun, J., Liu, J., et al. (2022) Maternal Secretin Ameliorates Obesity by Promoting White Adipose Tissue Browning in Offspring. EMBO Reports, 23, e54132. [Google Scholar] [CrossRef] [PubMed]
[57] He, Y., Liu, R.X., Zhu, M.T., et al. (2019) The Browning of White Adipose Tis-sue and Body Weight Loss in Primary Hyperparathyroidism. EBioMedicine, 40, 56-66. [Google Scholar] [CrossRef] [PubMed]
[58] Whitehead, A., Krause, F.N., Moran, A., et al. (2021) Brown and Beige Adi-pose Tissue Regulate Systemic Metabolism through a Metabolite Interorgan Signaling Axis. Nature Communications, 12, Article No. 1905. [Google Scholar] [CrossRef] [PubMed]
[59] Xiao, F., Jiang, H., Li, Z., et al. (2023) Reduced Hepatic Bradykinin Degrada-tion Accounts for Cold-Induced BAT Thermogenesis and WAT Browning in Male Mice. Nature Communications, 14, Article No. 2523. [Google Scholar] [CrossRef] [PubMed]
[60] Pydi, S.P., Jain, S., Tung, W., et al. (2019) Adipocyte Beta-Arrestin-2 Is Es-sential for Maintaining Whole Body Glucose and Energy Homeostasis. Nature Communications, 10, Article No. 2936. [Google Scholar] [CrossRef] [PubMed]
[61] Wu, T., Liu, Q., Li, Y., et al. (2021) Feeding-Induced Hepatokine, Manf, Ameliorates Diet-Induced Obesity by Promoting Adipose Browning via p38 MAPK Pathway. Journal of Experimental Medicine, 218, e20201203. [Google Scholar] [CrossRef] [PubMed]
[62] Bunk, J. and Kazak, L. (2022) Calcium Burns Beige. Journal of Experimental Medi-cine, 219, e20220382. [Google Scholar] [CrossRef] [PubMed]
[63] Cheung, W.W., Hao, S., Zheng, R., et al. (2021) Targeting Interleukin-1 for Revers-ing Fat Browning and Muscle Wasting in Infantile Nephropathic Cystinosis. Journal of Cachexia, Sarcopenia and Muscle, 12, 1296-1311. [Google Scholar] [CrossRef] [PubMed]
[64] Beppu, L.Y., Mooli, R.G.R., Qu, X., et al. (2021) Tregs Facilitate Obesity and Insulin Resistance via a Blimp-1/IL-10 Axis. JCI Insight, 6, e140644. [Google Scholar] [CrossRef] [PubMed]
[65] Abdullahi, A., Auger, C., Stanojcic, M., et al. (2019) Alternatively Activated Macrophages Drive Browning of White Adipose Tissue in Burns. An-nals of Surgery, 269, 554-563. [Google Scholar] [CrossRef
[66] Wang, Q., Li, H., Tajima, K., et al. (2022) Post-Translational Control of Beige Fat Biogenesis by PRDM16 Stabilization. Nature, 609, 151-158. [Google Scholar] [CrossRef] [PubMed]
[67] Wang, W., Ishibashi, J., Trefely, S., et al. (2019) A PRDM16-Driven Meta-bolic Signal from Adipocytes Regulates Precursor Cell Fate. Cell Metabolism, 30, 174-189 e5. [Google Scholar] [CrossRef] [PubMed]
[68] Zhao, S., Nie, T., Li, L., et al. (2023) Androgen Receptor Is a Negative Regula-tor of PRDM16 in Beige Adipocyte. Advanced Science, 10, e2300070. [Google Scholar] [CrossRef] [PubMed]
[69] Zhong, Y., Wang, Y., Li, X., et al. (2023) PRMT4 Facilitates White Adipose Tissue Browning and Thermogenesis by Methylating PPARgamma. Diabetes, 72, 1095-1111. [Google Scholar] [CrossRef] [PubMed]
[70] Xu, X., Krumm, C., So, J.S., et al. (2018) Preemptive Activa-tion of the Integrated Stress Response Protects Mice from Diet-Induced Obesity and Insulin Resistance by Fibroblast Growth Factor 21 Induction. Hepatology, 68, 2167-2181. [Google Scholar] [CrossRef] [PubMed]
[71] Fan, H., Zhang, Y., Zhang, J., et al. (2020) Cold-Inducible Klf9 Regulates Thermogene-sis of Brown and Beige Fat. Diabetes, 69, 2603-2618. [Google Scholar] [CrossRef] [PubMed]
[72] Ceddia, R.P., Zurawski, Z., Thompson Gray, A., et al. (2023) Gbetagamma-SNAP25 Exocytotic Brake Removal Enhances Insulin Action, Promotes Adipocyte Browning, and Protects against Diet-Induced Obesity. Journal of Clinical Investigation, 133, e160617. [Google Scholar] [CrossRef
[73] Nanduri, R., Furusawa, T., Lobanov, A., et al. (2022) Epigenetic Regulation of White Adipose Tissue Plasticity and Energy Metabolism by Nucleosome Binding HMGN Proteins. Nature Communications, 13, Article No. 7303. [Google Scholar] [CrossRef] [PubMed]
[74] Huang, L., Liu, P., Yang, Q., et al. (2022) The KRAB Domain-Containing Protein ZFP961 Represses Adipose Thermogenesis and Energy Expenditure through Interaction with PPARalpha. Advanced Science, 9, e2102949. [Google Scholar] [CrossRef] [PubMed]
[75] Rabiee, A., Plucinska, K., Isidor, M.S., et al. (2021) White Adipose Remodeling during Browning in Mice Involves YBX1 to Drive Thermogenic Commitment. Molecular Metabolism, 44, Article ID: 101137. [Google Scholar] [CrossRef] [PubMed]
[76] Solivan-Rivera, J., Yang Loureiro, Z., DeSouza, T., et al. (2022) A Neuro-genic Signature Involving Monoamine Oxidase—A Controls Human Thermogenic Adipose Tissue Development. Elife, 11, e78945. [Google Scholar] [CrossRef
[77] Li, B., Li, L., Li, M., et al. (2019) Microbiota Depletion Impairs Thermogenesis of Brown Adipose Tissue and Browning of White Adipose Tissue. Cell Reports, 26, 2720-2737e5. [Google Scholar] [CrossRef] [PubMed]
[78] Le Roy, T., Moens de Hase, E., Van Hul, M., et al. (2022) Dysosmobacter Welbionis Is a Newly Isolated Human Commensal Bacterium Preventing Diet-Induced Obesity and Metabolic Disorders in Mice. Gut, 71, 534-543. [Google Scholar] [CrossRef] [PubMed]
[79] Xu, Y., Wang, N., Tan, H.Y., et al. (2020) Panax Notoginseng Saponins Mod-ulate the Gut Microbiota to Promote Thermogenesis and Beige Adipocyte Reconstruction via Leptin-Mediated AMPKalpha/STAT3 Signaling in Diet-Induced Obesity. Theranostics, 10, 11302-11323. [Google Scholar] [CrossRef] [PubMed]
[80] Arias, N., Aguirre, L., Fernández-Quintela, A., et al. (2015) MicroRNAs Involved in the Browning Process of Adipocytes. Journal of Physiology and Biochemistry, 72, 509-521. [Google Scholar] [CrossRef] [PubMed]
[81] Yin, H., Pasut, A., Soleimani, V.D., et al. (2013) MicroRNA-133 Controls Brown Adipose Determination in Skeletal Muscle Satellite Cells by Targeting Prdm16. Cell Metabolism, 17, 210-224. [Google Scholar] [CrossRef] [PubMed]
[82] Sun, L., Xie, H., Mori, M.A., et al. (2011) Mir193b-365 Is Essential for Brown Fat Differentiation. Nature Cell Biology, 13, 958-965. [Google Scholar] [CrossRef] [PubMed]
[83] Kim, J., Okla, M., Erick-son, A., et al. (2016) Eicosapentaenoic Acid Potentiates Brown Thermogenesis through FFAR4-Dependent Up-Regulation of miR-30b and miR-378. Journal of Biological Chemistry, 291, 20551-20562. [Google Scholar] [CrossRef
[84] Pan, R. and Chen, Y. (2022) Latest Advancements on Combating Obesity by Targeting Human Brown/Beige Adipose Tissues. Frontiers in Endocrinology, 13, Article ID: 884944. [Google Scholar] [CrossRef] [PubMed]
[85] Cheung, W.W., Hao, S., Wang, Z., et al. (2020) Vitamin D Repletion Amelio-rates Adipose Tissue Browning and Muscle Wasting in Infantile Nephropathic Cystinosis-Associated Cachexia. Journal of Cachexia, Sarcopenia and Muscle, 11, 120-134. [Google Scholar] [CrossRef] [PubMed]
[86] Reilly, S.M., Abu-Odeh, M., Ameka, M., et al. (2021) FGF21 Is Required for the Metabolic Benefits of IKKepsilon/TBK1 Inhibition. Journal of Clinical Investigation, 131, e145546. [Google Scholar] [CrossRef
[87] Auger, C., Knuth, C.M., Abdullahi, A., et al. (2019) Metformin Prevents the Pathologi-cal Browning of Subcutaneous White Adipose Tissue. Molecular Metabolism, 29, 12-23. [Google Scholar] [CrossRef] [PubMed]
[88] Deng, J., Guo, Y., Yuan, F., et al. (2020) Autophagy Inhibition Prevents Glucocorticoid-Increased Adiposity via Suppressing BAT Whitening. Autophagy, 16, 451-465. [Google Scholar] [CrossRef] [PubMed]
[89] Cheng, L., Wang, J., An, Y., et al. (2022) Mulberry Leaf Activates Brown Adipose Tissue and Induces Browning of Inguinal White Adipose Tissue in Type 2 Diabetic Rats through Regulating AMP-Activated Protein Kinase Signalling Pathway. British Journal of Nutrition, 127, 810-822. [Google Scholar] [CrossRef
[90] Seoane-Collazo, P., Linares-Pose, L., Rial-Pensado, E., et al. (2019) Central Nicotine Induces Browning through Hypothalamic Kappa Opioid Receptor. Nature Communications, 10, Article No. 4037. [Google Scholar] [CrossRef] [PubMed]
[91] Knights, A.J., Vohralik, E.J., Houweling, P.J., et al. (2020) Eosinophil Func-tion in Adipose Tissue Is Regulated by Kruppel-Like Factor 3 (KLF3). Nature Communications, 11, Article No. 2922. [Google Scholar] [CrossRef] [PubMed]
[92] Hu, Y., Liu, L., Chen, Y., et al. (2023) Cancer-Cell-Secreted miR-204-5p Induces Leptin Signalling Pathway in White Adipose Tissue to Promote Cancer-Associated Cachexia. Nature Communications, 14, Article No. 5179. [Google Scholar] [CrossRef] [PubMed]
[93] Yuan, F., Jiang, H., Yin, H., et al. (2020) Activation of GCN2/ATF4 Signals in Amygdalar PKC-Delta Neurons Promotes WAT Browning under Leucine Deprivation. Nature Communications, 11, Article No. 2847. [Google Scholar] [CrossRef] [PubMed]
[94] Maliszewska, K. and Kretowski, A. (2021) Brown Adipose Tissue and Its Role in Insulin and Glucose Homeostasis. International Journal of Molecular Sciences, 22, Article No. 1530. [Google Scholar] [CrossRef] [PubMed]
[95] Tseng, Y.H. (2023) Adipose Tissue in Communication: Within and without. Nature Reviews Endocrinology, 19, 70-71. [Google Scholar] [CrossRef] [PubMed]
[96] Hwang, S. and Gao, B. (2019) How Does Your Fat Affect Your Liver When You Drink? Journal of Clinical Investigation, 129, 2181-2183. [Google Scholar] [CrossRef
[97] Roth, C.L., Molica, F. and Kwak, B.R. (2021) Browning of White Adipose Tissue as a Therapeutic Tool in the Fight against Atherosclerosis. Metabolites, 11, Article No. 319. [Google Scholar] [CrossRef] [PubMed]
[98] Doukbi, E., Soghomonian, A., Sengenes, C., et al. (2022) Browning Epicardial Adipose Tissue: Friend or Foe? Cells, 11, Article No. 991. [Google Scholar] [CrossRef] [PubMed]
[99] Petruzzelli, M., Schweiger, M., Schreiber, R., et al. (2014) A Switch from White to Brown Fat Increases Energy Expenditure in Cancer-Associated Cachexia. Cell Metabolism, 20, 433-447. [Google Scholar] [CrossRef] [PubMed]
[100] Anderson, L.J., Lee, J., Anderson, B., et al. (2022) Whole-Body and Adipose Tissue Metabolic Phenotype in Cancer Patients. Journal of Cachexia, Sarcopenia and Muscle, 13, 1124-1133. [Google Scholar] [CrossRef] [PubMed]
[101] Gaspar, R.C., Pauli, J.R., Shulman, G.I., et al. (2021) An Update on Brown Adipose Tissue Biology: A Discussion of Recent Findings. American Journal of Physiology: Endocrinology and Metabolism, 320, E488-E495. [Google Scholar] [CrossRef] [PubMed]