Absence of uncoupling protein 3 at thermoneutrality influences brown adipose tissue mitochondrial functionality in mice.

Szczegóły
Abstrakt

Tytuł:: Absence of uncoupling protein 3 at thermoneutrality influences brown adipose tissue mitochondrial functionality in mice.
Autorzy:: Silvestri E; Department of Science and Technology, University of Sannio, Benevento, Italy.
Senese R; Department of Environmental, Biological, and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Caserta, Italy.
De Matteis R; Department of Biomolecular Sciences, University of Urbino 'Carlo Bo', Urbino, Italy.
Cioffi F; Department of Science and Technology, University of Sannio, Benevento, Italy.
Moreno M; Department of Science and Technology, University of Sannio, Benevento, Italy.
Lanni A; Department of Environmental, Biological, and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Caserta, Italy.
Gentile A; Department of Biology, University of Naples Federico II, Naples, Italy.
Busiello RA; Department of Biology, University of Naples Federico II, Naples, Italy.
Salzano AM; Proteomics & Mass Spectrometry Laboratory, ISPAAM, National Research Council, Naples, Italy.
Scaloni A; Proteomics & Mass Spectrometry Laboratory, ISPAAM, National Research Council, Naples, Italy.
de Lange P; Department of Environmental, Biological, and Pharmaceutical Sciences and Technologies, University of Campania 'Luigi Vanvitelli', Caserta, Italy.
Goglia F; Department of Science and Technology, University of Sannio, Benevento, Italy.
Lombardi A; Department of Biology, University of Naples Federico II, Naples, Italy.
Źródło:: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2020 Nov; Vol. 34 (11), pp. 15146-15163. Date of Electronic Publication: 2020 Sep 18.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley
Original Publication: [Bethesda, Md.] : The Federation, [c1987-
MeSH Terms:: Oxidative Stress*
Thermogenesis*
Adipose Tissue, Brown/*pathology
Fatty Acids/*metabolism
Mitochondria/*pathology
Uncoupling Protein 3/*physiology
Adipose Tissue, Brown/metabolism ; Animals ; Energy Metabolism ; Female ; Homeostasis ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/metabolism ; Oxidation-Reduction
References:: Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84(1):277-359.
Bartelt A, Bruns OT, Reimer R, et al. Brown adipose tissue activity controls triglyceride clearance. Nat Med. 2011;17(2):200-205. https://doi.org/10.1038/nm.2297.
van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, et al. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009;360(15):1500-1508. Erratum. In: N Engl J Med. 2009 360(18):1917. https://doi.org/10.1056/NEJMoa0808718.
Nedergaard J, Bengtsson T, Cannon B. New powers of brown fat: fighting the metabolic syndrome. Cell Metab. 2011;13(3):238-240. https://doi.org/10.1016/j.cmet.2011.02.009.
Boss O, Farmer SR. Recruitment of brown adipose tissue as a therapy for obesity-associated diseases. Front Endocrinol (Lausanne). 2012;3:14. https://doi.org/10.3389/fendo.2012.00014.
Feldmann HM, Golozoubova V, Cannon B, Nedergaard J. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab. 2009;9(2):203-209. https://doi.org/10.1016/j.cmet.2008.12.014.
Masand R, Paulo E, Wu D, et al. Proteome imbalance of mitochondrial electron transport chain in brown adipocytes leads to metabolic benefits. Cell Metab. 2018;27(3):616-629.e4. https://doi.org/10.1016/j.cmet.2018.01.018.
Reitman ML. Of mice and men - environmental temperature, body temperature, and treatment of obesity. FEBS Lett. 2018;592(12):2098-2107. https://doi.org/10.1002/1873-3468.13070.
Hilse KE, Kalinovich AV, Rupprecht A, et al. The expression of UCP3 directly correlates to UCP1 abundance in brown adipose tissue. Biochim Biophys Acta. 2016;1857(1):72-78. https://doi.org/10.1016/j.bbabio.2015.10.011.
Pohl EE, Rupprecht A, Macher G, Hilse KE. Important trends in UCP3 Investigation. Front Physiol. 2019;10:470. https://doi.org/10.3389/fphys.2019.00470.
de Lange P, Lanni A, Beneduce L, et al. Uncoupling protein-3 is a molecular determinant for the regulation of resting metabolic rate by thyroid hormone. Endocrinology. 2001;142(8):3414-3420.
Enerbäck S, Jacobsson A, Simpson EM, et al. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature. 1997;387(6628):90-94.
Gong DW, Monemdjou S, Gavrilova O, et al. Lack of obesity and normal response to fasting and thyroid hormone in mice lacking uncoupling protein-3. J Biol Chem. 2000;275(21):16251-16257.
Mills EM, Banks ML, Sprague JE, Finkel T. Pharmacology: uncoupling the agony from ecstasy. Nature. 2003;426(6965):403-404.
Mills EM, Rusyniak DE, Sprague JE. The role of the sympathetic nervous system and uncoupling proteins in the thermogenesis induced by 3,4-methylenedioxymethamphetamine. J Mol Med (Berl). 2004;82(12):787-799.
Riley CL, Dao C, Kenaston MA, et al. The complementary and divergent roles of uncoupling proteins 1 and 3 in thermoregulation. J Physiol. 2016;594(24):7455-7464. https://doi.org/10.1113/JP272971.
Sprague JE, Mallett NM, Rusyniak DE, Mills E. UCP3 and thyroid hormone involvement in methamphetamine-induced hyperthermia. Biochem Pharmacol. 2004;68(7):1339-1343.
Nau K, Fromme T, Meyer CW, von Praun C, Heldmaier G, Klingenspor M. Brown adipose tissue specific lack of uncoupling protein 3 is associated with impaired cold tolerance and reduced transcript levels of metabolic genes. J Comp Physiol B. 2008;178(3):269-277.
Ozcan C, Palmeri M, Horvath TL, Russell KS, Russell RR 3rd. Role of uncoupling protein 3 in ischemia-reperfusion injury, arrhythmias, and preconditioning. Am J Physiol Heart Circ Physiol. 2013;304(9):H1192-H1200. https://doi.org/10.1152/ajpheart.00592.2012.
Perrino C, Schiattarella GG, Sannino A, et al. Genetic deletion of uncoupling protein 3 exaggerates apoptotic cell death in the ischemic heart leading to heart failure. J Am Heart Assoc. 2013;2(3):e000086. https://doi.org/10.1161/JAHA.113.000086.
Cadenas S. Mitochondrial uncoupling, ROS generation and cardioprotection. Biochim Biophys Acta Bioenerg. 2018;1859(9):940-950. https://doi.org/10.1016/j.bbabio.2018.05.019.
Busiello RA, Savarese S, Lombardi A. Mitochondrial uncoupling proteins and energy metabolism. Front Physiol. 2015;6:36. https://doi.org/10.3389/fphys.2015.00036.
Schrauwen P, Russell AP, Moonen-Kornips E, Boon N, Hesselink MK. Effect of 2 weeks of endurance training on uncoupling protein 3 content in untrained human subjects. Acta Physiol Scand. 2005;183(3):273-280.
Schrauwen P, Mensink M, Schaart G, et al. Reduced skeletal muscle uncoupling protein-3 content in prediabetic subjects and type 2 diabetic patients: restoration by rosiglitazone treatment. J Clin Endocrinol Metab. 2006;91(4):1520-1525.
Echtay KS, Roussel D, St-Pierre J, et al. Superoxide activates mitochondrial uncoupling proteins. Nature. 2002;415(6867):96-99.
Lombardi A, Busiello RA, Napolitano L, et al. UCP3 translocates lipid hydroperoxide and mediates lipid hydroperoxide-dependent mitochondrial uncoupling. J Biol Chem. 2010;285(22):16599-16605. https://doi.org/10.1074/jbc.M110.102699.
Milloux RJ, Harper ME. Uncoupling proteins and the control of mitochondrial reactive oxygen species production. Free Radic Biol Med. 2011;51(6):1106-1115. https://doi.org/10.1016/j.freeradbiomed.2011.06.022.
Senese R, Valli V, Moreno M, et al. Uncoupling protein 3 expression levels influence insulin sensitivity, fatty acid oxidation, and related signaling pathways. Pflugers Arch. 2011;461:153-164. https://doi.org/10.1007/s00424-010-0892-3.
Lombardi A, Busiello RA, De Matteis R, et al. Absence of uncoupling protein-3 at thermoneutrality impacts lipid handling and energy homeostasis in mice. Cells. 2019;8(8):E916. https://doi.org/10.3390/cells8080916.
Hilse KE, Rupprecht A, Egerbacher M, et al. The expression of uncoupling protein 3 coincides with the fatty acid oxidation type of metabolism in adult murine heart. Front Physiol. 2018;9:747. https://doi.org/10.3389/fphys.2018.00747.
Bloor ID, Symonds ME. Sexual dimorphism in white and brown adipose tissue with obesity and inflammation. Horm Behav. 2014;66(1):95-103. https://doi.org/10.1016/j.yhbeh.2014.02.007.
Choi DK, Oh TS, Choi JW, et al. Gender difference in proteome of brown adipose tissues between male and female rats exposed to a high fat diet. Cell Physiol Biochem. 2011;28(5):933-948. https://doi.org/10.1159/000335807.
Rodriguez-Cuenca S, Pujol E, Justo R, et al. Sex-dependent thermogenesis, differences in mitochondrial morphology and function, and adrenergic response in brown adipose tissue. J Biol Chem. 2002;277(45):42958-42963. https://doi.org/10.1074/jbc.M207229200.
Valle A, García-Palmer FJ, Oliver J, Roca P. Sex differences in brown adipose tissue thermogenic features during caloric restriction. Cell Physiol Biochem. 2007;19(1-4):195-204. https://doi.org/10.1159/000099207.
Heath RL, Tappel AL. A new sensitive assay for the measurement of hydroperoxides. Anal Biochem. 1976;76(1):184-191.
Clark AM, Sousa KM, Jennings C, MacDougald OA, Kennedy RT. Continuous-flow enzyme assay on a microfluidic chip for monitoring glycerol secretion from cultured adipocytes. Anal. Chem. 2009;81(6):2350-2356. https://doi.org/10.1021/ac8026965.
Akerman KE, Wikstrom MK. Safranine as a probe of the mitochondrial membrane potential. FEBS Lett. 1976;68:191-197.
Schagger H. Native electrophoresis for isolation of mitochondrial oxidative phosphorylation protein complexes. Methods Enzymol. 1995;260:190-202.
Lombardi A, Silvestri E, Cioffi F, et al. Defining the transcriptomic and proteomic profiles of rat ageing skeletal muscle by the use of a cDNA array, 2D- and Blue native-PAGE approach. J Proteomics. 2009;72(4):708-721.
Zerbetto E, Vergani L, Dabbeni-Sala F. Quantification of muscle mitochondrial oxidative phosphorylation enzymes via histochemical staining of blue native polyacrylamide gels. Electrophoresis. 1997;18(11):2059-2064.
Mráček T, Holzerová E, Drahota Z, et al. ROS generation and multiple forms of mammalian mitochondrial glycerol-3-phosphate dehydrogenase. Biochim Biophys Acta. 2014;1837(1):98-111. https://doi.org/10.1016/j.bbabio.2013.08.007.
Schägger H, Cramer WA, von Jagow G. Analysis of molecular masses and oligomeric states of protein complexes by blue native electrophoresis and isolation of membrane protein complexes by two-dimensional native electrophoresis. Anal Biochem. 1994;217(2):220-230.
Arioli S, Roncada P, Salzano AM, et al. The relevance of carbon dioxide metabolism in Streptococcus thermophilus. Microbiology. 2009;155(Pt 6):1953-1965. https://doi.org/10.1099/mic.0.024737-0.
Salzano AM, Novi G, Arioli S, Corona S, Mora D, Scaloni A. Mono-dimensional blue native-PAGE and bi-dimensional blue native/urea-PAGE or/SDS-PAGE combined with nLC-ESI-LIT-MS/MS unveil membrane protein heteromeric and homomeric complexes in Streptococcus thermophilus. J Proteomics. 2013;94:240-261. https://doi.org/10.1016/j.jprot.2013.09.007.
Mráček T, Drahota Z, Houštěk J. The function and the role of the mitochondrial glycerol-3-phosphate dehydrogenase in mammalian tissues. Biochim Biophys Acta. 2013;1827(3):401-410. https://doi.org/10.1016/j.bbabio.2012.11.014.
Garrib A, McMurray WC. Purification and characterization of glycerol-3-phosphate dehydrogenase (flavin-linked) from rat liver mitochondria. J Biol Chem. 1986;261(17):8042-8048.
Rauchová H, Drahota Z, Rauch P, Fato R, Lenaz G. Coenzyme Q releases the inhibitory effect of free fatty acids on mitochondrial glycerophosphate dehydrogenase. Acta Biochim Pol. 2003;50(2):405-413.
Bukowiecki LJ, Lindberg O. Control of sn-glycerol 3-phosphate oxidation in brown adipose tissue mitochondria by calcium and acyl-CoA. Biochim Biophys Acta. 1974;348(1):115-125.
De Marchi U, Castelbou C, Demaurex N. Uncoupling protein 3 (UCP3) modulates the activity of Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) by decreasing mitochondrial ATP production. J Biol Chem. 2011;286(37):32533-32541. https://doi.org/10.1074/jbc.M110.216044.
Motloch LJ, Gebing T, Reda S, Schwaiger A, Wolny M, Hoppe UC. UCP3 regulates single-channel activity of the cardiac mCa1. J Menbr Biol. 2016;249(4):577-584. https://doi.org/10.1007/s00232-016-9913-2.
Lenaz G, Genova ML. Supramolecular organisation of the mitochondrial respiratory chain: a new challenge for the mechanism and control of oxidative phosphorylation. Adv Exp Med Biol. 2012;748:107-144. https://doi.org/10.1007/978-1-4614-3573-0_5.
Miwa S, Brand MD. Mitochondrial matrix reactive oxygen species production is very sensitive to mild uncoupling. Biochem Soc Trans. 2003;31(Pt 6):1300-1301.
Miwa S, Brand MD. The topology of superoxide production by complex III and glycerol 3-phosphate dehydrogenase in Drosophila mitochondria. Biochim Biophys Acta. 2005;1709(3):214-219.
Vrbacký M, Drahota Z, Mrácek T, et al. Respiratory chain components involved in the glycerophosphate dehydrogenase-dependent ROS production by brown adipose tissue mitochondria. Biochim Biophys Acta. 2007;1767(7):989-997.
Orr AL, Quinlan CL, Perevoshchikova IV, Brand MD. A refined analysis of superoxide production by mitochondrial sn-glycerol 3-phosphate dehydrogenase. J Biol Chem. 2012;287(51):42921-42935. https://doi.org/10.1074/jbc.M112.397828.
Calderon-Dominguez M, Mir JF, Fucho R, Weber M, Serra D, Herrero L. Fatty acid metabolism and the basis of brown adipose tissue function. Adipocyte. 2015;5(2):98-118. https://doi.org/10.1080/21623945.2015.1122857.
Gonzalez-Hurtado E, Lee J, Choi J, Wolfgang MJ. Fatty acid oxidation is required for active and quiescent brown adipose tissue maintenance and thermogenic programing. Mol Metab. 2018;7:45-56. https://doi.org/10.1016/j.molmet.2017.11.004.
McBride S, Wei-LaPierre L, McMurray F, et al. Skeletal muscle mitoflashes, pH, and the role of uncoupling protein-3. Arch Biochem Biophys. 2019;663:239-248. https://doi.org/10.1016/j.abb.2019.01.018.
Friedman JR, Mourier A, Yamada J, McCaffery JM, Nunnari J. MICOS coordinates with respiratory complexes and lipids to establish mitochondrial inner membrane architecture. Elife. 2015;4:e07739. https://doi.org/10.7554/eLife.07739.
Quintana-Cabrera R, Mehrotra A, Rigoni G, Soriano ME. Who and how in the regulation of mitochondrial cristae shape and function. Biochem Biophys Res Commun. 2018;500(1):94-101. https://doi.org/10.1016/j.bbrc.2017.04.088.
He J, Ford HC, Carroll J, et al. Assembly of the membrane domain of ATP synthase in human mitochondria. Proc Natl Acad Sci U S A. 2018;115(12):2988-2993. https://doi.org/10.1073/pnas.1722086115.
Sztalryda C, Brasaemle DL. The perilipin family of lipid droplet proteins: Gatekeepers of intracellular lipolysis. Biochim Biophys Acta Mol Cell Biol Lipids. 2017;1862(10):1221-1232. https://doi.org/10.1016/j.bbalip.2017.07.009.
Contributed Indexing:: Keywords: metabolism; oxidative stress; respiratory chain
Substance Nomenclature:: 0 (Fatty Acids)
0 (Ucp3 protein, mouse)
0 (Uncoupling Protein 3)
Entry Date(s):: Date Created: 20200918 Date Completed: 20210427 Latest Revision: 20210427
Update Code:: 20240104
DOI:: 10.1096/fj.202000995R
PMID:: 32946628
: Czasopismo naukowe

The physiological role played by uncoupling protein 3 (UCP3) in brown adipose tissue (BAT) has not been fully elucidated so far. In the present study, we evaluated the impact of the absence of UCP3 on BAT mitochondrial functionality and morphology. To this purpose, wild type (WT) and UCP3 Knockout (KO) female mice were housed at thermoneutrality (30°C), a condition in which BAT contributes to energy homeostasis independently of its cold-induced thermogenic function. BAT mitochondria from UCP3 KO mice presented a lower ability to oxidize the fatty acids and glycerol-3-phosphate, and an enhanced oxidative stress as revealed by enhanced mitochondrial electron leak, lipid hydroperoxide levels, and induction of antioxidant mitochondrial enzymatic capacity. The absence of UCP3 also influenced the mitochondrial super-molecular protein aggregation, an important feature for fatty acid oxidation rate as well as for adequate cristae organization and mitochondrial shape. Indeed, electron microscopy revealed alterations in mitochondrial morphology in brown adipocytes from KO mice. In the whole, data here reported show that the absence of UCP3 results in a significant alteration of BAT mitochondrial physiology and morphology. These observations could also help to clarify some aspects of the association between metabolic disorders associated with low UCP3 levels, as previously reported in human studies.
(© 2020 Federation of American Societies for Experimental Biology.)

Informacja