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For: Tchoukalova Y, Koutsari C, Jensen M. Committed subcutaneous preadipocytes are reduced in human obesity. Diabetologia 2007;50:151-7. [PMID: 17096115 DOI: 10.1007/s00125-006-0496-9] [Citation(s) in RCA: 85] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2006] [Accepted: 09/07/2006] [Indexed: 01/03/2023]

For:	Tchoukalova Y, Koutsari C, Jensen M. Committed subcutaneous preadipocytes are reduced in human obesity. Diabetologia 2007;50:151-7. [PMID: 17096115 DOI: 10.1007/s00125-006-0496-9] [Citation(s) in RCA: 85] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2006] [Accepted: 09/07/2006] [Indexed: 01/03/2023]

Number

Cited by Other Article(s)

Singh R, Madruga LYC, Savargaonkar A, Martins AF, Kipper MJ, Popat KC. Tanfloc-Modified Titanium Surfaces: Optimizing Blood Coagulant Activity and Stem Cell Compatibility. ACS Biomater Sci Eng 2025;11:1445-1455. [PMID: 40013664 PMCID: PMC11897940 DOI: 10.1021/acsbiomaterials.4c02106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 02/20/2025] [Accepted: 02/24/2025] [Indexed: 02/28/2025]

Plissonneau C, Santosa S. Regional primary preadipocyte characteristics in humans with obesity and type 2 diabetes mellitus. Heliyon 2024;10:e39710. [PMID: 39553621 PMCID: PMC11564010 DOI: 10.1016/j.heliyon.2024.e39710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 10/21/2024] [Accepted: 10/21/2024] [Indexed: 11/19/2024] Open

Singh R, Madruga LYC, Savargaonkar A, Martins AF, Kipper MJ, Popat KC. COVALENT GRAFTING OF TANFLOC ON TITANIA NANOTUBE ARRAYS: AN APPROACH TO MITIGATE BACTERIAL ADHESION AND IMPROVE THE ANTIBACTERIAL EFFICACY OF TITANIUM IMPLANTS. ADVANCED MATERIALS INTERFACES 2024;11:2400406. [PMID: 40248746 PMCID: PMC12002416 DOI: 10.1002/admi.202400406] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Indexed: 04/19/2025]

Liermann-Wooldrik KT, Kosmacek EA, Oberley-Deegan RE. Adipose Tissues Have Been Overlooked as Players in Prostate Cancer Progression. Int J Mol Sci 2024;25:12137. [PMID: 39596205 PMCID: PMC11594286 DOI: 10.3390/ijms252212137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Revised: 11/07/2024] [Accepted: 11/10/2024] [Indexed: 11/28/2024] Open

Rosell-Moll E, My NTK, Balbuena-Pecino S, Montblanch M, Rodríguez I, Gutiérrez J, Garcia de la Serrana D, Capilla E, Navarro I. Morphofunctional characterization of the three main adipose tissue depots in rainbow trout (Oncorhynchus mykiss). Comp Biochem Physiol B Biochem Mol Biol 2024;275:111039. [PMID: 39396638 DOI: 10.1016/j.cbpb.2024.111039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 10/09/2024] [Accepted: 10/09/2024] [Indexed: 10/15/2024]

Mo YY, Han YX, Xu SN, Jiang HL, Wu HX, Cai JM, Li L, Bu YH, Xiao F, Liang HD, Wen Y, Liu YZ, Yin YL, Zhou HD. Adipose Tissue Plasticity: A Comprehensive Definition and Multidimensional Insight. Biomolecules 2024;14:1223. [PMID: 39456156 PMCID: PMC11505740 DOI: 10.3390/biom14101223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 09/24/2024] [Accepted: 09/25/2024] [Indexed: 10/28/2024] Open

Affiliation(s)

Yu-Yao Mo National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.-Y.M.); (Y.-X.H.); (S.-N.X.); (H.-L.J.); (H.-X.W.); (J.-M.C.); (L.L.); (F.X.); (H.-D.L.); (Y.W.)
Yu-Xin Han National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.-Y.M.); (Y.-X.H.); (S.-N.X.); (H.-L.J.); (H.-X.W.); (J.-M.C.); (L.L.); (F.X.); (H.-D.L.); (Y.W.)
Shi-Na Xu National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.-Y.M.); (Y.-X.H.); (S.-N.X.); (H.-L.J.); (H.-X.W.); (J.-M.C.); (L.L.); (F.X.); (H.-D.L.); (Y.W.)
Hong-Li Jiang National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.-Y.M.); (Y.-X.H.); (S.-N.X.); (H.-L.J.); (H.-X.W.); (J.-M.C.); (L.L.); (F.X.); (H.-D.L.); (Y.W.)
Hui-Xuan Wu National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.-Y.M.); (Y.-X.H.); (S.-N.X.); (H.-L.J.); (H.-X.W.); (J.-M.C.); (L.L.); (F.X.); (H.-D.L.); (Y.W.)
Jun-Min Cai National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.-Y.M.); (Y.-X.H.); (S.-N.X.); (H.-L.J.); (H.-X.W.); (J.-M.C.); (L.L.); (F.X.); (H.-D.L.); (Y.W.)
Long Li National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.-Y.M.); (Y.-X.H.); (S.-N.X.); (H.-L.J.); (H.-X.W.); (J.-M.C.); (L.L.); (F.X.); (H.-D.L.); (Y.W.)
Yan-Hong Bu Department of Blood Transfusion, The Second Xiangya Hospital, Central South University, Changsha 410012, China;
Fen Xiao National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.-Y.M.); (Y.-X.H.); (S.-N.X.); (H.-L.J.); (H.-X.W.); (J.-M.C.); (L.L.); (F.X.); (H.-D.L.); (Y.W.)
Han-Dan Liang National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.-Y.M.); (Y.-X.H.); (S.-N.X.); (H.-L.J.); (H.-X.W.); (J.-M.C.); (L.L.); (F.X.); (H.-D.L.); (Y.W.)
Ying Wen National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.-Y.M.); (Y.-X.H.); (S.-N.X.); (H.-L.J.); (H.-X.W.); (J.-M.C.); (L.L.); (F.X.); (H.-D.L.); (Y.W.)
Yu-Ze Liu Pediatric Cardiac Surgery Centre, Fuwai Hospital, National Centre for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China;
Yu-Long Yin Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China
Hou-De Zhou National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, China; (Y.-Y.M.); (Y.-X.H.); (S.-N.X.); (H.-L.J.); (H.-X.W.); (J.-M.C.); (L.L.); (F.X.); (H.-D.L.); (Y.W.)

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Yang Z, Chen F, Zhang Y, Ou M, Tan P, Xu X, Li Q, Zhou S. Therapeutic targeting of white adipose tissue metabolic dysfunction in obesity: mechanisms and opportunities. MedComm (Beijing) 2024;5:e560. [PMID: 38812572 PMCID: PMC11134193 DOI: 10.1002/mco2.560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Revised: 04/09/2024] [Accepted: 04/14/2024] [Indexed: 05/31/2024] Open

Gambaro SE, Zubiría MG, Giordano AP, Castro PF, Garraza C, Harnichar AE, Alzamendi A, Spinedi E, Giovambattista A. Role of Spexin in White Adipose Tissue Thermogenesis under Basal and Cold-Stimulated Conditions. Int J Mol Sci 2024;25:1767. [PMID: 38339044 PMCID: PMC10855774 DOI: 10.3390/ijms25031767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 01/24/2024] [Accepted: 01/30/2024] [Indexed: 02/12/2024] Open

Affiliation(s)

Sabrina E. Gambaro Neuroendocrinology Laboratory, Multidisciplinary Institute of Cellular Biology (IMBICE, CICPBA-CONICET-UNLP), La Plata 1900, Argentina; (S.E.G.); (M.G.Z.); (A.P.G.); (P.F.C.); (C.G.); (A.E.H.); (A.A.) Biology Department, School of Exact Sciences, La Plata National University, La Plata 1900, Argentina
María G. Zubiría Neuroendocrinology Laboratory, Multidisciplinary Institute of Cellular Biology (IMBICE, CICPBA-CONICET-UNLP), La Plata 1900, Argentina; (S.E.G.); (M.G.Z.); (A.P.G.); (P.F.C.); (C.G.); (A.E.H.); (A.A.) Biology Department, School of Exact Sciences, La Plata National University, La Plata 1900, Argentina
Alejandra P. Giordano Neuroendocrinology Laboratory, Multidisciplinary Institute of Cellular Biology (IMBICE, CICPBA-CONICET-UNLP), La Plata 1900, Argentina; (S.E.G.); (M.G.Z.); (A.P.G.); (P.F.C.); (C.G.); (A.E.H.); (A.A.) Biology Department, School of Exact Sciences, La Plata National University, La Plata 1900, Argentina
Patricia F. Castro Neuroendocrinology Laboratory, Multidisciplinary Institute of Cellular Biology (IMBICE, CICPBA-CONICET-UNLP), La Plata 1900, Argentina; (S.E.G.); (M.G.Z.); (A.P.G.); (P.F.C.); (C.G.); (A.E.H.); (A.A.)
Carolina Garraza Neuroendocrinology Laboratory, Multidisciplinary Institute of Cellular Biology (IMBICE, CICPBA-CONICET-UNLP), La Plata 1900, Argentina; (S.E.G.); (M.G.Z.); (A.P.G.); (P.F.C.); (C.G.); (A.E.H.); (A.A.)
Alejandro E. Harnichar Neuroendocrinology Laboratory, Multidisciplinary Institute of Cellular Biology (IMBICE, CICPBA-CONICET-UNLP), La Plata 1900, Argentina; (S.E.G.); (M.G.Z.); (A.P.G.); (P.F.C.); (C.G.); (A.E.H.); (A.A.)
Ana Alzamendi Neuroendocrinology Laboratory, Multidisciplinary Institute of Cellular Biology (IMBICE, CICPBA-CONICET-UNLP), La Plata 1900, Argentina; (S.E.G.); (M.G.Z.); (A.P.G.); (P.F.C.); (C.G.); (A.E.H.); (A.A.)
Eduardo Spinedi CENEXA (UNLP-CONICET), La Plata Medical School-UNLP, Calles 60 y 120, La Plata 1900, Argentina;
Andrés Giovambattista Neuroendocrinology Laboratory, Multidisciplinary Institute of Cellular Biology (IMBICE, CICPBA-CONICET-UNLP), La Plata 1900, Argentina; (S.E.G.); (M.G.Z.); (A.P.G.); (P.F.C.); (C.G.); (A.E.H.); (A.A.) Biology Department, School of Exact Sciences, La Plata National University, La Plata 1900, Argentina

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Kar A, Alvarez M, Garske KM, Huang H, Lee SHT, Deal M, Das SS, Koka A, Jamal Z, Mohlke KL, Laakso M, Heinonen S, Pietiläinen KH, Pajukanta P. Age-dependent genes in adipose stem and precursor cells affect regulation of fat cell differentiation and link aging to obesity via cellular and genetic interactions. Genome Med 2024;16:19. [PMID: 38297378 PMCID: PMC10829214 DOI: 10.1186/s13073-024-01291-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 01/19/2024] [Indexed: 02/02/2024] Open

Abstract

BACKGROUND

Age and obesity are dominant risk factors for several common cardiometabolic disorders, and both are known to impair adipose tissue function. However, the underlying cellular and genetic factors linking aging and obesity on adipose tissue function have remained elusive. Adipose stem and precursor cells (ASPCs) are an understudied, yet crucial adipose cell type due to their deterministic adipocyte differentiation potential, which impacts the capacity to store fat in a metabolically healthy manner.

METHODS

We integrated subcutaneous adipose tissue (SAT) bulk (n=435) and large single-nucleus RNA sequencing (n=105) data with the UK Biobank (UKB) (n=391,701) data to study age-obesity interactions originating from ASPCs by performing cell-type decomposition, differential expression testing, cell-cell communication analyses, and construction of polygenic risk scores for body mass index (BMI).

RESULTS

We found that the SAT ASPC proportions significantly decrease with age in an obesity-dependent way consistently in two independent cohorts, both showing that the age dependency of ASPC proportions is abolished by obesity. We further identified 76 genes (72 SAT ASPC marker genes and 4 transcription factors regulating ASPC marker genes) that are differentially expressed by age in SAT and functionally enriched for developmental processes and adipocyte differentiation (i.e., adipogenesis). The 76 age-perturbed ASPC genes include multiple negative regulators of adipogenesis, such as RORA, SMAD3, TWIST2, and ZNF521, form tight clusters of longitudinally co-expressed genes during human adipogenesis, and show age-based differences in cellular interactions between ASPCs and adipose cell types. Finally, our genetic data demonstrate that cis-regional variants of these genes interact with age as predictors of BMI in an obesity-dependent way in the large UKB, while no such gene-age interaction on BMI is observed with non-age-dependent ASPC marker genes, thus independently confirming our cellular ASPC results at the biobank level.

CONCLUSIONS

Overall, we discover that obesity prematurely induces a decrease in ASPC proportions and identify 76 developmentally important ASPC genes that implicate altered negative regulation of fat cell differentiation as a mechanism for aging and directly link aging to obesity via significant cellular and genetic interactions.

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Affiliation(s)

Asha Kar Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA
Marcus Alvarez Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA
Kristina M Garske Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA
Huiling Huang Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA Bioinformatics Interdepartmental Program, UCLA, Los Angeles, USA
Seung Hyuk T Lee Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA
Milena Deal Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA
Sankha Subhra Das Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA
Amogha Koka Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA
Zoeb Jamal Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA
Karen L Mohlke Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Markku Laakso Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
Sini Heinonen Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
Kirsi H Pietiläinen Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland HealthyWeightHub, Endocrinology, Abdominal Center, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland
Päivi Pajukanta Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles (UCLA), Gonda Center, Room 6357B, 695 Charles E. Young Drive South, Los Angeles, CA, 90095-7088, USA. Bioinformatics Interdepartmental Program, UCLA, Los Angeles, USA. Institute for Precision Health, David Geffen School of Medicine at UCLA, Los Angeles, USA.

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Carobbio S, Pellegrinelli V, Vidal-Puig A. Adipose Tissue Dysfunction Determines Lipotoxicity and Triggers the Metabolic Syndrome: Current Challenges and Clinical Perspectives. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024;1460:231-272. [PMID: 39287854 DOI: 10.1007/978-3-031-63657-8_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]

Abstract

The adipose tissue organ is organised as distinct anatomical depots located all along the body axis, and it is constituted of three different types of adipocytes: white, beige and brown, which are integrated with vascular, immune, neural, and extracellular stroma cells. These distinct adipocytes serve different specialised functions. The main function of white adipocytes is to ensure healthy storage of excess nutrients/energy and its rapid mobilisation to supply the demand of energy imposed by physiological cues in other organs, whereas brown and beige adipocytes are designed for heat production through uncoupling lipid oxidation from energy production. The concerted action of the three types of adipocytes/tissues ensures an optimal metabolic status. However, when one or several of these adipose depots become dysfunctional because of sustained lipid/nutrient overload, then insulin resistance and associated metabolic complications ensue. These metabolic alterations close a vicious cycle that negatively affects the adipose tissue functionality and compromises global metabolic homeostasis. Optimising white adipose tissue expandability and ensuring its functional metabolic flexibility and/or promoting brown/beige mediated thermogenic activity are complementary strategies that counteract obesity and its associated lipotoxic metabolic effects. However, the development of these therapeutic approaches requires a deep understanding of adipose tissue in all broad aspects. In this chapter, we will discuss the characteristics of the different adipose tissue depots with respect to origins and precursors recruitment, plasticity, cellular composition, and expandability capacity potential as well as molecular and metabolic characteristic signatures in both physiological and pathophysiological conditions. Current antilipotoxic strategies for future clinical application are also discussed in this chapter.

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Scheidl TB, Brightwell AL, Easson SH, Thompson JA. Maternal obesity and programming of metabolic syndrome in the offspring: searching for mechanisms in the adipocyte progenitor pool. BMC Med 2023;21:50. [PMID: 36782211 PMCID: PMC9924890 DOI: 10.1186/s12916-023-02730-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Accepted: 01/09/2023] [Indexed: 02/15/2023] Open

Oh S, Kim HM, Batsukh S, Sun HJ, Kim T, Kang D, Son KH, Byun K. High-Intensity Focused Ultrasound Induces Adipogenesis via Control of Cilia in Adipose-Derived Stem Cells in Subcutaneous Adipose Tissue. Int J Mol Sci 2022;23:ijms23168866. [PMID: 36012125 PMCID: PMC9408610 DOI: 10.3390/ijms23168866] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 07/30/2022] [Accepted: 08/07/2022] [Indexed: 11/16/2022] Open

Ye RZ, Richard G, Gévry N, Tchernof A, Carpentier AC. Fat Cell Size: Measurement Methods, Pathophysiological Origins, and Relationships With Metabolic Dysregulations. Endocr Rev 2022;43:35-60. [PMID: 34100954 PMCID: PMC8755996 DOI: 10.1210/endrev/bnab018] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Indexed: 11/19/2022]

Thyroid hormone receptor alpha sumoylation modulates white adipose tissue stores. Sci Rep 2021;11:24105. [PMID: 34916557 PMCID: PMC8677787 DOI: 10.1038/s41598-021-03491-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Accepted: 12/01/2021] [Indexed: 11/20/2022] Open

Gavin KM, Sullivan TM, Maltzahn JK, Rahkola JT, Acosta AS, Kohrt WM, Majka SM, Klemm DJ. Hematopoietic stem cells produce intermediate lineage adipocyte progenitors that simultaneously express both myeloid and mesenchymal lineage markers in adipose tissue. Adipocyte 2021;10:394-407. [PMID: 34404315 PMCID: PMC8381847 DOI: 10.1080/21623945.2021.1957290] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open

Affiliation(s)

Kathleen M. Gavin Eastern Colorado Veterans Administration Geriatric Research, Education and Clinical Center (GRECC), Rocky Mountain Regional VA Medical Center, Aurora, CO, USA Division of Geriatric Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Timothy M. Sullivan Eastern Colorado Veterans Administration Geriatric Research, Education and Clinical Center (GRECC), Rocky Mountain Regional VA Medical Center, Aurora, CO, USA Cardiovascular Pulmonary Research Laboratory, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Joanne K. Maltzahn Eastern Colorado Veterans Administration Geriatric Research, Education and Clinical Center (GRECC), Rocky Mountain Regional VA Medical Center, Aurora, CO, USA Cardiovascular Pulmonary Research Laboratory, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Jeremy T. Rahkola Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Rocky Mountain Regional VA Medical Center, Aurora, CO, USA
Alistair S. Acosta Flow Cytometry Shared Resource, University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Wendy M. Kohrt Eastern Colorado Veterans Administration Geriatric Research, Education and Clinical Center (GRECC), Rocky Mountain Regional VA Medical Center, Aurora, CO, USA Division of Geriatric Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Susan M. Majka Cardiovascular Pulmonary Research Laboratory, University of Colorado Anschutz Medical Campus, Aurora, CO, USA Division of Pulmonary, Critical Care and Sleep Medicine, Department of Biomedical Research, National Jewish Health, Denver, CO, USA Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Dwight J. Klemm Eastern Colorado Veterans Administration Geriatric Research, Education and Clinical Center (GRECC), Rocky Mountain Regional VA Medical Center, Aurora, CO, USA Cardiovascular Pulmonary Research Laboratory, University of Colorado Anschutz Medical Campus, Aurora, CO, USA Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

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Mikolajczak A, Sallam NA, Singh RD, Scheidl TB, Walsh EJ, Larion S, Huang C, Thompson JA. Accelerated developmental adipogenesis programs adipose tissue dysfunction and cardiometabolic risk in offspring born to dams with metabolic dysfunction. Am J Physiol Endocrinol Metab 2021;321:E581-E591. [PMID: 34459218 PMCID: PMC8791794 DOI: 10.1152/ajpendo.00229.2021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]

Reyes-Farias M, Fos-Domenech J, Serra D, Herrero L, Sánchez-Infantes D. White adipose tissue dysfunction in obesity and aging. Biochem Pharmacol 2021;192:114723. [PMID: 34364887 DOI: 10.1016/j.bcp.2021.114723] [Citation(s) in RCA: 121] [Impact Index Per Article: 30.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/30/2021] [Accepted: 08/03/2021] [Indexed: 12/19/2022]

Björk C, Subramanian N, Liu J, Acosta JR, Tavira B, Eriksson AB, Arner P, Laurencikiene J. An RNAi Screening of Clinically Relevant Transcription Factors Regulating Human Adipogenesis and Adipocyte Metabolism. Endocrinology 2021;162:6272286. [PMID: 33963396 PMCID: PMC8197287 DOI: 10.1210/endocr/bqab096] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Indexed: 12/13/2022]

Zou P, Wang F, Wang J, Lu Y, Tran D, Seo SK. Impact of injection sites on clinical pharmacokinetics of subcutaneously administered peptides and proteins. J Control Release 2021;336:310-321. [PMID: 34186147 DOI: 10.1016/j.jconrel.2021.06.038] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 05/28/2021] [Accepted: 06/24/2021] [Indexed: 01/26/2023]

Abstract

For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection sites are often not available and the underlying mechanisms that may affect SC absorption have not been systematically investigated. In this study, we surveyed clinical PK data (AUC, C_max, and T_max) for SC administered drug products including therapeutic proteins and peptides based on literature and FDA database. The PK data after abdominal injection was used as a reference to determine the relative bioavailability of SC injections to the arm and thigh. The survey retrieved 19 immunoglobulin G (IgGs), 18 peptides/small proteins (molecular weight < 16 kDa), and 8 non-IgG proteins that had available clinical PK data from multiple SC injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides/small proteins, and 3 (38%) non-IgG proteins, exhibited injection site-dependent PK (i.e. PK differed by injection sites). Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (T_max ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low T_max are associated with high risk of injection site-dependent SC absorption. IgGs with T_1/2 < 15 days or T_max < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs.

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Felix JB, Cox AR, Hartig SM. Acetyl-CoA and Metabolite Fluxes Regulate White Adipose Tissue Expansion. Trends Endocrinol Metab 2021;32:320-332. [PMID: 33712368 PMCID: PMC8035226 DOI: 10.1016/j.tem.2021.02.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 02/21/2021] [Accepted: 02/22/2021] [Indexed: 12/29/2022]

Koc M, Wald M, Varaliová Z, Ondrůjová B, Čížková T, Brychta M, Kračmerová J, Beranová L, Pala J, Šrámková V, Šiklová M, Gojda J, Rossmeislová L. Lymphedema alters lipolytic, lipogenic, immune and angiogenic properties of adipose tissue: a hypothesis-generating study in breast cancer survivors. Sci Rep 2021;11:8171. [PMID: 33854130 PMCID: PMC8046998 DOI: 10.1038/s41598-021-87494-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Accepted: 03/30/2021] [Indexed: 12/26/2022] Open

Abstract

Later stages of secondary lymphedema are associated with the massive deposition of adipose tissue (AT). The factors driving lymphedema-associated AT (LAT) expansion in humans remain rather elusive. We hypothesized that LAT expansion could be based on alterations of metabolic, adipogenic, immune and/or angiogenic qualities of AT. AT samples were acquired from upper limbs of 11 women with unilateral breast cancer-related lymphedema and 11 healthy women without lymphedema. Additional control group of 11 female breast cancer survivors without lymphedema was used to assess systemic effects of lymphedema. AT was analysed for adipocyte size, lipolysis, angiogenesis, secretion of cytokines, immune and stem cell content and mRNA gene expression. Further, adipose precursors were isolated and tested for their proliferative and adipogenic capacity. The effect of undrained LAT- derived fluid on adipogenesis was also examined. Lymphedema did not have apparent systemic effect on metabolism and cytokine levels, but it was linked with higher lymphocyte numbers and altered levels of several miRNAs in blood. LAT showed higher basal lipolysis, (lymph)angiogenic capacity and secretion of inflammatory cytokines when compared to healthy AT. LAT contained more activated CD4+ T lymphocytes than healthy AT. mRNA levels of (lymph)angiogenic markers were deregulated in LAT and correlated with markers of lipolysis. In vitro, adipose cells derived from LAT did not differ in their proliferative, adipogenic, lipogenic and lipolytic potential from cells derived from healthy AT. Nevertheless, exposition of preadipocytes to LAT-derived fluid improved their adipogenic conversion when compared with the effect of serum. This study presents results of first complex analysis of LAT from upper limb of breast cancer survivors. Identified LAT alterations indicate a possible link between (lymph)angiogenesis and lipolysis. In addition, our in vitro results imply that AT expansion in lymphedema could be driven partially by exposition of adipose precursors to undrained LAT-derived fluid.

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Affiliation(s)

Michal Koc Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic
Martin Wald Department of Surgery, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague 5, Czech Republic
Zuzana Varaliová Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic
Barbora Ondrůjová Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic
Terezie Čížková Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic
Milan Brychta Department of Radiotherapy and Oncology, Kralovske Vinohrady University Hospital, Prague 10, Czech Republic
Jana Kračmerová Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic
Lenka Beranová Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic
Jan Pala Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic
Veronika Šrámková Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic.,Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague 10, Czech Republic
Michaela Šiklová Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic.,Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague 10, Czech Republic
Jan Gojda Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague 10, Czech Republic.,Second Internal Medicine Department, Kralovske Vinohrady University Hospital, Prague 10, Czech Republic
Lenka Rossmeislová Department of Pathophysiology, Centre for Research On Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruská 87, 100 00, Prague 10, Czech Republic. .,Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague 10, Czech Republic.

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Adipose stem cells in obesity: challenges and opportunities. Biosci Rep 2021;40:225001. [PMID: 32452515 PMCID: PMC7284323 DOI: 10.1042/bsr20194076] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 05/08/2020] [Accepted: 05/22/2020] [Indexed: 02/07/2023] Open

Extracellular Vesicles from Adipose Tissue Stem Cells in Diabetes and Associated Cardiovascular Disease; Pathobiological Impact and Therapeutic Potential. Int J Mol Sci 2020;21:ijms21249598. [PMID: 33339409 PMCID: PMC7766415 DOI: 10.3390/ijms21249598] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/11/2020] [Accepted: 12/14/2020] [Indexed: 02/07/2023] Open

Murphy J, Delaney KZ, Dam V, Tam BT, Khor N, Tsoukas MA, Morais JA, Santosa S. Sex Affects Regional Variations in Subcutaneous Adipose Tissue T Cells but not Macrophages in Adults with Obesity. Obesity (Silver Spring) 2020;28:2310-2314. [PMID: 33179451 DOI: 10.1002/oby.23039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 08/09/2020] [Accepted: 09/01/2020] [Indexed: 12/16/2022]

Affiliation(s)

Jessica Murphy Department of Health, Kinesiology, and Applied Physiology, Concordia University, Montreal, Quebec, Canada Metabolism, Obesity, and Nutrition Laboratory, PERFORM Centre, Concordia University, Montreal, Quebec, Canada Centre de recherche - Axe maladies chroniques, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Ile-de-Montréal, Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada
Kerri Z Delaney Department of Health, Kinesiology, and Applied Physiology, Concordia University, Montreal, Quebec, Canada Metabolism, Obesity, and Nutrition Laboratory, PERFORM Centre, Concordia University, Montreal, Quebec, Canada Centre de recherche - Axe maladies chroniques, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Ile-de-Montréal, Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada
Vi Dam Department of Health, Kinesiology, and Applied Physiology, Concordia University, Montreal, Quebec, Canada Metabolism, Obesity, and Nutrition Laboratory, PERFORM Centre, Concordia University, Montreal, Quebec, Canada Centre de recherche - Axe maladies chroniques, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Ile-de-Montréal, Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada
Bjorn T Tam Department of Health, Kinesiology, and Applied Physiology, Concordia University, Montreal, Quebec, Canada Metabolism, Obesity, and Nutrition Laboratory, PERFORM Centre, Concordia University, Montreal, Quebec, Canada Centre de recherche - Axe maladies chroniques, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Ile-de-Montréal, Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada
Natalie Khor Metabolism, Obesity, and Nutrition Laboratory, PERFORM Centre, Concordia University, Montreal, Quebec, Canada
Michael A Tsoukas Division of Endocrinology, Department of Medicine, McGill University, Royal Victoria Hospital, MUHC Glen site, Montreal, Quebec, Canada
José A Morais Department of Health, Kinesiology, and Applied Physiology, Concordia University, Montreal, Quebec, Canada Division of Geriatric Medicine, Department of Medicine, McGill University, MUHC-Montreal General Hospital, Montreal, Quebec, Canada
Sylvia Santosa Department of Health, Kinesiology, and Applied Physiology, Concordia University, Montreal, Quebec, Canada Metabolism, Obesity, and Nutrition Laboratory, PERFORM Centre, Concordia University, Montreal, Quebec, Canada Centre de recherche - Axe maladies chroniques, Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Ile-de-Montréal, Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada

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Dadson P, Rebelos E, Honka H, Juárez-Orozco LE, Kalliokoski KK, Iozzo P, Teuho J, Salminen P, Pihlajamäki J, Hannukainen JC, Nuutila P. Change in abdominal, but not femoral subcutaneous fat CT-radiodensity is associated with improved metabolic profile after bariatric surgery. Nutr Metab Cardiovasc Dis 2020;30:2363-2371. [PMID: 32919861 DOI: 10.1016/j.numecd.2020.07.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Revised: 07/07/2020] [Accepted: 07/08/2020] [Indexed: 02/07/2023]

Abstract

BACKGROUND AND AIMS

Computed tomography (CT)-derived adipose tissue radiodensity represents a potential noninvasive surrogate marker for lipid deposition and obesity-related metabolic disease risk. We studied the effects of bariatric surgery on CT-derived adipose radiodensities in abdominal and femoral areas and their relationships to circulating metabolites in morbidly obese patients.

METHODS AND RESULTS

We examined 23 morbidly obese women who underwent CT imaging before and 6 months after bariatric surgery. Fifteen healthy non-obese women served as controls. Radiodensities of the abdominal subcutaneous (SAT) and visceral adipose tissue (VAT), and the femoral SAT, adipose tissue masses were measured in all participants. Circulating metabolites were measured by NMR. At baseline, radiodensities of abdominal fat depots were lower in the obese patients as compared to the controls. Surprisingly, radiodensity of femoral SAT was higher in the obese as compared to the controls. In the abdominal SAT depot, radiodensity strongly correlated with SAT mass (r = -0.72, p < 0.001). After surgery, the radiodensities of abdominal fat increased significantly (both p < 0.01), while femoral SAT radiodensity remained unchanged. Circulating ApoB/ApoA-I, leucine, valine, and GlycA decreased, while glycine levels significantly increased as compared to pre-surgical values (all p < 0.05). The increase in abdominal fat radiodensity correlated negatively with the decreased levels of ApoB/ApoA-I ratio, leucine and GlycA (all p < 0.05). The increase in abdominal SAT density was significantly correlated with the decrease in the fat depot mass (r = -0.66, p = 0.002).

CONCLUSION

Higher lipid content in abdominal fat depots, and lower content in femoral subcutaneous fat, constitute prominent pathophysiological features in morbid obesity. Further studies are needed to clarify the role of non-abdominal subcutaneous fat in the pathogenesis of obesity.

CLINICAL TRIAL REGISTRATION NUMBER

NCT01373892.

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BMP7 overexpression in adipose tissue induces white adipogenesis and improves insulin sensitivity in ob/ob mice. Int J Obes (Lond) 2020;45:449-460. [PMID: 33110143 DOI: 10.1038/s41366-020-00700-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 08/26/2020] [Accepted: 10/14/2020] [Indexed: 02/06/2023]

Saha PK, Hamilton MP, Rajapakshe K, Putluri V, Felix JB, Masschelin P, Cox AR, Bajaj M, Putluri N, Coarfa C, Hartig SM. miR-30a targets gene networks that promote browning of human and mouse adipocytes. Am J Physiol Endocrinol Metab 2020;319:E667-E677. [PMID: 32799658 PMCID: PMC7864240 DOI: 10.1152/ajpendo.00045.2020] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]

Abstract

MicroRNA-30a (miR-30a) impacts adipocyte function, and its expression in white adipose tissue (WAT) correlates with insulin sensitivity in obesity. Bioinformatic analysis demonstrates that miR-30a expression contributes to 2% of all miRNA expression in human tissues. However, molecular mechanisms of miR-30a function in fat cells remain unclear. Here, we expanded our understanding of how miR-30a expression contributes to antidiabetic peroxisome proliferator-activated receptor-γ (PPARγ) agonist activity and metabolic functions in adipocytes. We found that WAT isolated from diabetic patients shows reduced miR-30a levels and diminished expression of the canonical PPARγ target genes ADIPOQ and FABP4 relative to lean counterparts. In human adipocytes, miR-30a required PPARγ for maximal expression, and the PPARγ agonist rosiglitazone robustly induced miR-30a but not other miR-30 family members. Transcriptional activity studies in human adipocytes also revealed that ectopic expression of miR-30a enhanced the activity of rosiglitazone coupled with higher expression of fatty acid and glucose metabolism markers. Diabetic mice that overexpress ectopic miR-30a in subcutaneous WAT display durable reductions in serum glucose and insulin levels for more than 30 days. In agreement with our in vitro findings, RNA-seq coupled with Gene Set Enrichment Analysis (GSEA) suggested that miR-30a enabled activation of the beige fat program in vivo, as evidenced by enhanced mitochondrial biogenesis and induction of UCP1 expression. Metabolomic and gene expression profiling established that the long-term effects of ectopic miR-30a expression enable accelerated glucose metabolism coupled with subcutaneous WAT hyperplasia. Together, we establish a putative role of miR-30a in mediating PPARγ activity and advancing metabolic programs of white to beige fat conversion.

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Vishvanath L, Gupta RK. Contribution of adipogenesis to healthy adipose tissue expansion in obesity. J Clin Invest 2020;129:4022-4031. [PMID: 31573549 DOI: 10.1172/jci129191] [Citation(s) in RCA: 368] [Impact Index Per Article: 73.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open

Cruz MM, Simão JJ, de Sá RDCC, Farias TSM, da Silva VS, Abdala F, Antraco VJ, Armelin-Correa L, Alonso-Vale MIC. Palmitoleic Acid Decreases Non-alcoholic Hepatic Steatosis and Increases Lipogenesis and Fatty Acid Oxidation in Adipose Tissue From Obese Mice. Front Endocrinol (Lausanne) 2020;11:537061. [PMID: 33117273 PMCID: PMC7561405 DOI: 10.3389/fendo.2020.537061] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Accepted: 08/28/2020] [Indexed: 01/06/2023] Open

Abstract

We recently demonstrated that palmitoleic acid (C16:1n7), a monounsaturated fatty acid, increases the metabolic and oxidative capacity of 3T3-L1 adipocytes. Herein, the effect of 16:1n7 supplementation on metabolic parameters on white adipose tissue (WAT) and liver of obese mice induced by a high-fat diet (HFD) was addressed by analyzing metabolic (dys)function and altered genes expression in adipose tissue, as well as liver and serum biochemistry analysis. For this purpose, mice were induced to obesity for 8 weeks, and from the 5th week, they received 16:1n7 (300 mg/kg per day) or water for 30 days, by gavage. Subcutaneous inguinal (ING) and epididymal (EPI) WAT were removed for analysis of metabolic, (anti)inflammatory, adipogenic, and thermogenic genes expression by real-time reverse transcriptase-polymerase chain reaction. Additionally, metabolic activities of isolated adipocytes, such as glucose uptake, lipogenesis (triacylglycerol esterification), β-oxidation, and lipolysis in ING adipocytes, were also assessed. Despite the higher fat intake, the HFD group showed lower food intake but higher body weight, increased glucose, significant dyslipidemia, and increased liver and adipose depot mass, accompanied by liver steatosis. The 16:1n7 supplementation slowed down the body mass gain and prevented the increase of lipids in the liver. HFD+n7 animals presented increased fatty acid oxidation and lipogenesis compared to control, but no effect was observed on lipolysis and glucose uptake in ING isolated adipocytes. Besides, 16:1n7 increased the content of the mRNA encoding FABP4, but partially prevented the expression of genes encoding ATGL, HSL, perilipin, lipin, C/EBP-α, PPAR-γ, C/EBP-β, CPT1, NRF1, TFAM, PRDM16, and nitric oxide synthase 2 in ING depot from HFD group of animals. Finally, HFD increased Mcp1 and Tnfα expression, and 16:1n7 promoted a more marked increase in it. In summary, the data show that palmitoleic acid promotes metabolic changes and partially prevents the increase in gene expression on adipocytes triggered by obesity, suggesting that HFD+n7 animals do not require the same magnitude of metabolic adaptation to cope with energy demand from the HFD. In the long term, the effects of 16:1n7 may be more evident and beneficial for the function/dysfunction of WAT from an obese organism, with relevant repercussions in the systemic metabolic homeostasis.

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Affiliation(s)

Maysa M. Cruz Post-graduate Program in Chemical Biology – Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
Jussara J. Simão Post-graduate Program in Chemical Biology – Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
Roberta D. C. C. de Sá Post-graduate Program in Chemical Biology – Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
Talita S. M. Farias Post-graduate Program in Chemical Biology – Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
Viviane S. da Silva Post-graduate Program in Chemical Biology – Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
Fernanda Abdala Department of Biological Sciences, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
Vitor J. Antraco Post-graduate Program in Chemical Biology – Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
Lucia Armelin-Correa Post-graduate Program in Chemical Biology – Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil Department of Biological Sciences, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil
Maria Isabel C. Alonso-Vale Post-graduate Program in Chemical Biology – Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil Department of Biological Sciences, Institute of Environmental Sciences, Chemical and Pharmaceutical, Federal University of São Paulo - UNIFESP, Diadema, Brazil *Correspondence: Maria Isabel C. Alonso-Vale

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Vyas KS, Bole M, Vasconez HC, Banuelos JM, Martinez-Jorge J, Tran N, Lemaine V, Mardini S, Bakri K. Profile of Adipose-Derived Stem Cells in Obese and Lean Environments. Aesthetic Plast Surg 2019;43:1635-1645. [PMID: 31267153 DOI: 10.1007/s00266-019-01397-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2018] [Accepted: 05/04/2019] [Indexed: 12/17/2022]

Schaar A, Sun Y, Sukumaran P, Rosenberger TA, Krout D, Roemmich JN, Brinbaumer L, Claycombe-Larson K, Singh BB. Ca²⁺ entry via TRPC1 is essential for cellular differentiation and modulates secretion via the SNARE complex. J Cell Sci 2019;132:jcs.231878. [PMID: 31182642 PMCID: PMC6633397 DOI: 10.1242/jcs.231878] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 05/27/2019] [Indexed: 12/17/2022] Open

Cox AR, Chernis N, Masschelin PM, Hartig SM. Immune Cells Gate White Adipose Tissue Expansion. Endocrinology 2019;160:1645-1658. [PMID: 31107528 PMCID: PMC6591013 DOI: 10.1210/en.2019-00266] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Accepted: 05/14/2019] [Indexed: 12/15/2022]

White JD, Dewal RS, Stanford KI. The beneficial effects of brown adipose tissue transplantation. Mol Aspects Med 2019;68:74-81. [PMID: 31228478 DOI: 10.1016/j.mam.2019.06.004] [Citation(s) in RCA: 84] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Revised: 02/20/2019] [Accepted: 06/18/2019] [Indexed: 01/02/2023]

Jiang N, Li Y, Shu T, Wang J. Cytokines and inflammation in adipogenesis: an updated review. Front Med 2019;13:314-329. [PMID: 30066061 DOI: 10.1007/s11684-018-0625-0] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Accepted: 12/12/2017] [Indexed: 02/07/2023]

Silva KR, Baptista LS. Adipose-derived stromal/stem cells from different adipose depots in obesity development. World J Stem Cells 2019;11:147-166. [PMID: 30949294 PMCID: PMC6441940 DOI: 10.4252/wjsc.v11.i3.147] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Revised: 01/27/2019] [Accepted: 02/28/2019] [Indexed: 02/06/2023] Open

Elucidating the Preadipocyte and Its Role in Adipocyte Formation: a Comprehensive Review. Stem Cell Rev Rep 2018;14:27-42. [PMID: 29027120 DOI: 10.1007/s12015-017-9774-9] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]

Sadie-Van Gijsen H. Adipocyte biology: It is time to upgrade to a new model. J Cell Physiol 2018;234:2399-2425. [PMID: 30192004 DOI: 10.1002/jcp.27266] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 07/25/2018] [Indexed: 12/15/2022]

Adipose Tissue Function and Expandability as Determinants of Lipotoxicity and the Metabolic Syndrome. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017;960:161-196. [PMID: 28585199 DOI: 10.1007/978-3-319-48382-5_7] [Citation(s) in RCA: 130] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Pérez LM, de Lucas B, Lunyak VV, Gálvez BG. Adipose stem cells from obese patients show specific differences in the metabolic regulators vitamin D and Gas5. Mol Genet Metab Rep 2017;12:51-56. [PMID: 28580301 PMCID: PMC5447652 DOI: 10.1016/j.ymgmr.2017.05.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 05/22/2017] [Indexed: 12/21/2022] Open

Cox-York KA, Erickson CB, Pereira RI, Bessesen DH, Van Pelt RE. Region-specific effects of oestradiol on adipose-derived stem cell differentiation in post-menopausal women. J Cell Mol Med 2016;21:677-684. [PMID: 27862950 PMCID: PMC5345675 DOI: 10.1111/jcmm.13011] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Accepted: 09/18/2016] [Indexed: 12/25/2022] Open

Zubiría MG, Alzamendi A, Moreno G, Portales A, Castrogiovanni D, Spinedi E, Giovambattista A. Relationship between the Balance of Hypertrophic/Hyperplastic Adipose Tissue Expansion and the Metabolic Profile in a High Glucocorticoids Model. Nutrients 2016;8:nu8070410. [PMID: 27384583 PMCID: PMC4963886 DOI: 10.3390/nu8070410] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Revised: 05/27/2016] [Accepted: 06/14/2016] [Indexed: 12/12/2022] Open

Pellegrinelli V, Carobbio S, Vidal-Puig A. Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues. Diabetologia 2016;59:1075-88. [PMID: 27039901 PMCID: PMC4861754 DOI: 10.1007/s00125-016-3933-4] [Citation(s) in RCA: 291] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Accepted: 02/23/2016] [Indexed: 02/07/2023]

Myneni VD, Melino G, Kaartinen MT. Transglutaminase 2--a novel inhibitor of adipogenesis. Cell Death Dis 2015;6:e1868. [PMID: 26313919 PMCID: PMC4558519 DOI: 10.1038/cddis.2015.238] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Revised: 06/12/2015] [Accepted: 07/22/2015] [Indexed: 12/22/2022]

Fried SK, Lee MJ, Karastergiou K. Shaping fat distribution: New insights into the molecular determinants of depot- and sex-dependent adipose biology. Obesity (Silver Spring) 2015;23:1345-52. [PMID: 26054752 PMCID: PMC4687449 DOI: 10.1002/oby.21133] [Citation(s) in RCA: 117] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2015] [Revised: 04/01/2015] [Accepted: 04/03/2015] [Indexed: 12/14/2022]

Silva KR, Liechocki S, Carneiro JR, Claudio-da-Silva C, Maya-Monteiro CM, Borojevic R, Baptista LS. Stromal-vascular fraction content and adipose stem cell behavior are altered in morbid obese and post bariatric surgery ex-obese women. Stem Cell Res Ther 2015;6:72. [PMID: 25884374 PMCID: PMC4435525 DOI: 10.1186/s13287-015-0029-x] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2014] [Revised: 01/29/2015] [Accepted: 03/02/2015] [Indexed: 12/11/2022] Open

Abstract

INTRODUCTION

Subcutaneous adipose tissue is an interesting source of autologous stem cells with a fundamental role in the pathophysiology of obesity, metabolic syndromes and insulin resistance. We hypothesize that obesity could alter the stromal-vascular fraction (SVF) and adipose stem cell (ASCs) functions, which could compromise its regenerative behavior. Furthermore, we aimed to evaluate whether ASCs derived from post bariatric surgery ex-obese women maintain their functions in a similar fashion as do those from individuals who have never been obese.

METHODS

The SVF of subcutaneous adipose tissue from control (n = 6, body mass index - BMI - 27.5 ± 0.5 kg/m(2)), obese (n = 12, BMI 46.2 ± 5.1 kg/m(2)) and post bariatric surgery ex-obese (n = 7, initial BMI 47.8 ± 1.3 kg/m(2); final BMI 28.1 ± 1.1 kg/m(2)) women were isolated and evaluated by flow cytometry. ASCs were tested for lipid accumulation by perilipin, adipose differentiation-related protein (ADRP) and Oil Red O staining after adipogenic stimulus. The cytokines secreted by the ASCs and after lipid accumulation induction were also evaluated.

RESULTS

The subcutaneous adipose tissue of obese and post bariatric surgery ex-obese women was enriched in pericytes (p = 0.0345). The number of supra-adventitial cells was not altered in the obese patients, but it was highly enriched in the post bariatric surgery ex-obese women (p = 0.0099). The ASCs of the post bariatric surgery ex-obese patients secreted more MCP-1 (monocyte chemoattractant protein-1; p = 0.0078). After lipid accumulation induction, the ASCs of the patients in all groups secreted less IL-6 than the ASCs with no adipogenic stimulus (p < 0.0001). Obese ASCs with lipid accumulation secreted the highest amount of IL-6 (p < 0.001) whereas the ASCs from the controls secreted the highest amount of adiponectin (p < 0.0001). The ASCs from the post bariatric surgery ex-obese patients showed the highest levels of lipid accumulation whereas those from the obese women had the lowest levels (p < 0.0001).

CONCLUSIONS

SVF content and ASC behavior are altered in the subcutaneous adipose tissue of morbid obese women; these changes are not completely restored after bariatric surgery-induced weight loss. The cellular alterations described in this study could affect the regenerative effects of adipose stem cells. Further investigations are required to avoid jeopardizing the development of autologous stem cell-based therapies.

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Affiliation(s)

Karina R Silva Programa de Pós-graduação em Clínica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil. .,Núcleo Multidisciplinar de Pesquisa UFRJ - Xerém em Biologia (Numpex-Bio), Universidade Federal do Rio de Janeiro, Polo Xerém, Duque de Caxias, RJ 25245-390, Brazil. .,Programa de Bioengenharia, Diretoria de Programas, Instituto Nacional de Metrologia, Qualidade e Tecnologia (Inmetro), Duque de Caxias, RJ 25250-020, Brazil.
Sally Liechocki Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ 21.040-900, Brazil.
João R Carneiro Departamento de Nutrologia do Hospital Universitário Clementino Fraga Filho, Universidade Fereal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil.
Cesar Claudio-da-Silva Serviço de Cirurgia Plástica, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil.
Clarissa M Maya-Monteiro Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ 21.040-900, Brazil.
Radovan Borojevic Programa de Pós-graduação em Clínica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil. .,Programa de Bioengenharia, Diretoria de Programas, Instituto Nacional de Metrologia, Qualidade e Tecnologia (Inmetro), Duque de Caxias, RJ 25250-020, Brazil.
Leandra S Baptista Programa de Pós-graduação em Clínica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-913, Brazil. .,Núcleo Multidisciplinar de Pesquisa UFRJ - Xerém em Biologia (Numpex-Bio), Universidade Federal do Rio de Janeiro, Polo Xerém, Duque de Caxias, RJ 25245-390, Brazil. .,Programa de Bioengenharia, Diretoria de Programas, Instituto Nacional de Metrologia, Qualidade e Tecnologia (Inmetro), Duque de Caxias, RJ 25250-020, Brazil.

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Ota A, Kovary KM, Wu OH, Ahrends R, Shen WJ, Costa MJ, Feldman BJ, Kraemer FB, Teruel MN. Using SRM-MS to quantify nuclear protein abundance differences between adipose tissue depots of insulin-resistant mice. J Lipid Res 2015;56:1068-78. [PMID: 25840986 PMCID: PMC4409283 DOI: 10.1194/jlr.d056317] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2014] [Indexed: 01/14/2023] Open

Varlamov O, Chu M, Cornea A, Sampath H, Roberts CT. Cell-autonomous heterogeneity of nutrient uptake in white adipose tissue of rhesus macaques. Endocrinology 2015;156:80-9. [PMID: 25356825 PMCID: PMC4272393 DOI: 10.1210/en.2014-1699] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]

Du L, Fan H, Miao H, Zhao G, Hou Y. Extremely low frequency magnetic fields inhibit adipogenesis of human mesenchymal stem cells. Bioelectromagnetics 2014;35:519-30. [DOI: 10.1002/bem.21873] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2014] [Accepted: 07/14/2014] [Indexed: 11/09/2022]

Bunner AE, Chandrasekera PC, Barnard ND. Knockout mouse models of insulin signaling: Relevance past and future. World J Diabetes 2014;5:146-159. [PMID: 24748928 PMCID: PMC3990311 DOI: 10.4239/wjd.v5.i2.146] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2013] [Revised: 01/03/2014] [Accepted: 02/20/2014] [Indexed: 02/05/2023] Open

Rogers C, Davis B, Neufer PD, Murphy MP, Anderson EJ, Robidoux J. A transient increase in lipid peroxidation primes preadipocytes for delayed mitochondrial inner membrane permeabilization and ATP depletion during prolonged exposure to fatty acids. Free Radic Biol Med 2014;67:330-41. [PMID: 24269897 PMCID: PMC3935619 DOI: 10.1016/j.freeradbiomed.2013.11.012] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2013] [Revised: 10/29/2013] [Accepted: 11/12/2013] [Indexed: 12/22/2022]

Abstract

Preadipocytes are periodically subjected to fatty acid (FA) concentrations that are potentially cytotoxic. We tested the hypothesis that prolonged exposure of preadipocytes of human origin to a physiologically relevant mix of FAs leads to mitochondrial inner membrane (MIM) permeabilization and ultimately to mitochondrial crisis. We found that exposure of preadipocytes to FAs led to progressive cyclosporin A-sensitive MIM permeabilization, which in turn caused a reduction in MIM potential, oxygen consumption, and ATP synthetic capacity and, ultimately, death. Additionally, we showed that FAs induce a transient increase in intramitochondrial reactive oxygen species (ROS) and lipid peroxide production, lasting roughly 30 and 120min for the ROS and lipid peroxides, respectively. MIM permeabilization and its deleterious consequences including mitochondrial crisis and cell death were prevented by treating the cells with the mitochondrial FA uptake inhibitor etomoxir, the mitochondrion-selective superoxide and lipid peroxide antioxidants MitoTempo and MitoQ, or the lipid peroxide and reactive carbonyl scavenger l-carnosine. FAs also promoted a delayed oxidative stress phase. However, the beneficial effects of etomoxir, MitoTempo, and l-carnosine were lost by delaying the treatment by 2h, suggesting that the initial phase was sufficient to prime the cells for the delayed MIM permeabilization and mitochondrial crisis. It also suggested that the second ROS production phase is a consequence of this loss in mitochondrial health. Altogether, our data suggest that approaches designed to diminish intramitochondrial ROS or lipid peroxide accumulation, as well as MIM permeabilization, are valid mechanism-based therapeutic avenues to prevent the loss in preadipocyte metabolic fitness associated with prolonged exposure to elevated FA levels.

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