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(WAT) of pool tissue unlimited adipose White Crepnigauthor: *Corresponding Abbreviations: Society g Nutrition the of Proceedings kltlmsl n ie n a edt nui resist- insulin in to metabolism lead may lipid and and Chronically- liver ance diabetes. and glucose 2 muscle type alter skeletal and obesity NEFA in elevated case metabolism, the normal only is with Over- as interfere not molecules. can are signalling NEFA also of NEFA are abundance tissues. they glycerol source, other are energy one and by an bloodstream uptake and the for into NEFA available released are energy-rich which three molecule, to molecule aehlmnsadisln(i.1.Tehormone The 1). (Fig. insulin and catecholamines 8 A,daygyeos AP at cdbnigpoen S,hroesniielps;L,lpddolt G,mnaygyeo iae PK, ; monoacylglycerol MGL, droplet; lipid LD, lipase; hormone-sensitive tissue. HSL, adipose protein; white WAT, acid-binding perilipin; fatty PLIN, FABP, kinase; protein diacylglycerols; DAG, 58; etn fteNtiinScey otdb h ctihScin a eda h oa oit fEibrh dnug n7and 7 on Edinburgh Edinburgh, of Society Royal the at held was Section, Scottish the by hosted Society, Nutrition the of Meeting A ih euaoycnrlo ioyi spoie by provided is lipolysis of control regulatory Tight h uhr 09Frtpbihdoln 4Ags 2009 August 24 online published First 2009 Authors The 2 (2) https://www.cambridge.org/core Universite . omnlrglto faioyelipolysis adipocyte of regulation Hormonal 3 MK M-ciae rti iae R deegcrcpos TL dps A iae G-8 oprtv eeidentification gene comparative CGI-58, lipase; TAG adipose ATGL, receptors; adrenergic AR, kinase; protein AMP-activated AMPK, aoaor eBohme ntttFe Institut Biochimie, de Laboratoire ´ (1) eTuos,US ntttd Me de Institut UPS, Toulouse, de enovo de ioyi stebekono n TAG one of breakdown the is Lipolysis . 1 nemU5,Lbrtied ehrhssrlsObe les sur Recherches de Laboratoire U858, Inserm nowoeaioetsu eaoimadisssei fet sas rsne ntecnetof context the in presented also is adipose effects resistance. in findings systemic insulin these involved its of and and pathways Integration inflammation metabolism states. and tissue dynamic metabolic partners adipose pres- various a whole numerous under The of into interaction the lipolysis. that their over of to and control overview lipolysis revamped lipolysis. regulatory tissue an appropriately stimulated offers provides been and itself interactions review has basal in and droplet ent of that lipid cofactors regulation organelle inert , lipo- the highly-structured an to the and new of central of of idea are Knowledge dated identification that tissue. The to lipids tremendous the under- adipose and years central with to and proteins 15 relating are grown between past avenues developed it has the several control Over machinery in in resistance. that lytic made burden insulin mechanisms been and increasing has the obesity progress an and of aetiology mass are the tissue elucidating complications Adipose its countries. developed and obesity Human . https://doi.org/10.1017/S0029665109990279 rfso oiiu agn fax Langin, Dominique Professor euaino dps iselplssrevisited lipolysis tissue adipose of Regulation ypsu n‘rnir naioetsu biology’ tissue adipose in ‘Frontiers on Symposium ytei r trda A in TAG as stored are synthesis . IPaddress: Ve (2009), ´ 170.106.39.137 oi Be ronic dps ise ioyi:Lps:Lpddroplet Lipid Lipase: Lipolysis: tissue: Adipose 68 5–6 doi:10.1017/S0029665109990279 350–360 , ´ , on zaire ´ + 08 Oct2021 at06:28:31 eieMole decine 351263 mi [email protected] email 561325623, 33 ´ de 1,2 ´ ai eBooi ePra,F309Tuos,France Toulouse, F-31059 Purpan, de Biologie de ratif pi 2009 April 8 n oiiu Langin Dominique and ´ uar eRnui,IR5,F342Tuos,France Toulouse, F-31432 IFR150, Rangueil, de culaire noeiyi huh orsl rmacnutdstimulation accentuated from result to of thought is pro- obesity in the cAMP by pro-lipolytic and dictated a of is action effects lipolysis combined cyclase AR-dependent Thus, adenylyl duction. The receptors. inhibit protein latter GTP-binding inhibitory to coupling a nii ioyi i h ciainof activation the perilipin via catecholamines lipolysis protein Conversely, inhibit lipolysis. can LD-coating hormone- stimulate and phosphorylates to activates (PLIN) (HSL) which cAMP lipase A, in sensitive (PK) rise kinase A cyclase, protein production. adenylyl cAMP activate increasing receptors protein GTP-binding of Coupling of stimulate (AR). activation receptors the noradrenaline through neurotransmitter lipolysis and adrenaline K ciain hs napspada tt nui not insulin state postprandial a reduces acti- in consequently Thus, 3B and activation. cAMP, PKA to degrades insulin which leads to vation, binding 1 Insulin substrate adipocytes. on receptor receptor its to ing , subjectto theCambridgeCore termsofuse,available at -R mareti K-tmltdlplssobserved lipolysis PKA-stimulated in Impairment 2-AR. a 2-AR ´ site (3–5) ´ ,F342Tuos,France Toulouse, F-31432 s, nui lorgltslplsswe bind- when lipolysis regulates also Insulin . 1,2,3 * b -and 1- b b A n anti-lipolytic and -AR -and 1- b -Rt stimulatory to 2-AR a -Radtheir and 2-AR b 2-adrenergic https://www.cambridge.org/core/terms Downloaded from Proceedings of the Nutrition Society ciiy(i.1.Rssi GPatvt K,which PKG, activate PLIN cGMP and HSL in phosphorylates Rises PKA to cyclase 1). similarly guanylyl intrinsic (Fig. possess is activity which receptors, insulin, bind A peptides and Natriuretic type events. catecholamines pro-lipolytic in of implicated independent mini- pathway, also but adipocytes. storage in and breakdown TAG uptake mizes substrate favours only antd ota fctcoaie n sparticularly similar is of and is catecholamines peptides exercise of during natriuretic pronounced that by to lipolysis magnitude of lation eae S a huh ob h aelmtn tpin cofactors step lipases, other rate-limiting that the established three be now approximately is to For It thought lipolysis. of years. was regulation 10 HSL the past decades in the made over been lipolysis has progress Tremendous still is relevance physiological and anti-lipolytic the PG unknown. of which adenosine, wealth for catecholamines, machinery a metabolites by lipolytic also activated is or systems There pathways growth earlier. signalling described as the such adipo- altering factors human TNF and in hormone, lipolysis hormones of Additional control cytes. regulatory main the nhmnftclsa diinlsga transduction signal additional an cells fat human In aruei etds aehlmnsadislnprovide insulin and catecholamines peptides, Natriuretic https://www.cambridge.org/core iae nlplssregulation lipolysis in Lipases a n L6as nunelplssby lipolysis influence also IL-6 and , . https://doi.org/10.1017/S0029665109990279 β idn rti;G,ihbtr T-idn rti;IS nui eetrsbtae PI3-K GTP- substrate; droplet. stimulatory receptor lipid Gs, insulin LD, cyclase; hormonally-regulated. IRS, guanylyl monoacylglycerol protein; directly GC, and kinase; GTP-binding be (ATGL) phosphate inhibitory to phosphatidylinositol-3 lipase hormone-sensitive Gi, thought TAG phosphorylate protein; not Adipose PKG binding (PLINA). are and A PKA (MGL) (PKA) perilipin receptor. lipase A A and kinase type (HSL) accumulation via protein lipase cGMP and promote activation and B peptides PKG (PK) (AC) Natriuretic kinase and activity. protein cyclase of (PDE-3B) adenylyl activation 3B through by phosphodiesterase degradation cAMP production favours Insulin cAMP activation. inhibit and late ioyi.Culn of Coupling lipolysis. 1. Fig. 1/2 -AR (7,8) inltasuto ahasipiae nhroa oto fhmnadipocyte human of control hormonal in implicated pathways transduction Signal . IPaddress: . α 170.106.39.137 2 -AR b euaino dps iselplssrvstd351 revisited lipolysis tissue adipose of Regulation PDE-3B 1 PI3-K receptor Insulin PKB and cAMP b 2 (6) , on ( b Stimu- . 1/2 08 Oct2021 at06:28:31

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(45,46) (36,43) nvivo in hl t silencing its while A trg and storage TAG , n aa n iso- and basal and srqie for required is (56) (56–59) (52) 122 ,is , . https://www.cambridge.org/core/terms Downloaded from Proceedings of the Nutrition Society nacoigPIAt LD to PLINA anchoring in LN om hsclbriraon Dt euelipase reduce to LD around access barrier physical a forms PLINA hsgntp,btrte increased rather but genotype, this ucin,icuigpriiaini inltransduction signal in participation including functions, aelnrslsi h omto fivgntoson invaginations of formation the membranes of in expression cellular ectopic results that such caveolin structures these for protein aeleaesalivgntoso elpam mem- plasma cell on invaginations branes small are Caveolae stimulated fragmentation in promoting and lipases LD. 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CGI-58 PKA-stimulated of and importance basal to vant ail ipre otectsl neetrvril with reversible event an of cytosol, addition the the to dispersed rapidly ye G-8i oaie otesraeo Dvaasso- via LD of surface the PLINA to with localized ciation is CGI-58 cytes ain fCI5 aebe dnie nptet with patients in identified been syndrome have Chanarin-Dorfman CGI-58 of tations G-8 LN n TLi aa n PKA-stimulated and basal in ATGL and PLINA CGI-58, hrceie yteacmlto fanral large organs several abnormally in of LD accumulation of the amounts disorder a by syndrome, Chanarin-Dorfman characterized the of gene phospholipid causal overall content. lipid neutral increases reduces CGI-58 it yeast while content, Thus, ATGL. in of activator overexpression an as functions its a eetybe on oeetlspopaii acid lysophosphatidic exert to found activity been acyltransferase recently has n olwrlvl nlvr kn iny er,stomach, heart, kidney, skin, liver, testes, in lung and WAT levels and in lower In expressed to activity. highly and lipase is lacks serine CGI-58 usual therefore mouse the the itself of in place CGI-58 in residue. asparagine an contains CGI-58 ntectsli epnet cetae lipolysis accentuated to response in cytosol the in eetvl ciaigATGL activating selectively nlss hscmlxtasoae oL nPAacti- PKA on LD to transfer translocates energy vation complex resonance this fluorescence analysis, by demonstrated hnrnDrmnsnrm on uain r not interactions weak display are and PLIN expected mutations with as LD point to recruited syndrome Chanarin-Dorfman n ed omgaet ml LD accentuated small to greatly migrate is to tends co-localization and ATGL and CGI-58 opoieslblt oNF n aiiaeterintra- their mem- facilitate and and metabolic branes NEFA between to trafficking cellular solubility provide to okn oanfrFABP4 for domain docking vivo in nhmnsbet G-8hsbe dnie sa as identified been has CGI-58 subjects human In , subjectto theCambridgeCore termsofuse,available at (86) (83,84) (38) h rt30aioaiso S rvd a provide HSL of acids amino 300 first The . (88) . a h rcs hl-eldnmc involving dynamics whole-cell precise The . (90) / oprtv eeietfiain58 identification gene Comparative AP hsclybnst HSL to binds physically FABP4 . G-8siuae ioyi yptnl and potently by lipolysis stimulates CGI-58 . b hdoaefl-otiigpoenta re- that protein fold-containing -hydrolase hsotoemyb hsooial rele- physiologically be may outcome This . at cdbnigpoen4 protein acid-binding Fatty (87) b A naoit.Udrteeconditions these Under antagonists. -AR oee,tepttv aayi ra of triad catalytic putative the However, . (88,90) (91) a .On hsatvt sidpnetof independent is activity This . / b (20) hdoaedomain-containing -hydrolase (89) (92,93) b S n AP id1:1 bind FABP4 and HSL . A tmlto G-8is CGI-58 stimulation -AR nmtr uieadipo- murine mature In . (64) (81,82) G-8mtnswith mutants CGI-58 . (92) neetnl,CGI-58 Interestingly, . nttl iemu- nine total, In . APaethought are FABP . nvitro in (85) .As and https://www.cambridge.org/core/terms Downloaded from Proceedings of the Nutrition Society dnie TLit lipolysis into ATGL human identified of model hypothetical a PKA-stimulated drastically lipolysis. presents and adipocyte 2 basal have of Fig. model interactions lipolysis. working protein– lipid–protein the novel changed of and co- characterization its the and protein as lipase well additional as an activator, of identification recent The appears states. CGI-58 both but in elucidated important fully been not have lipolysis Be V. 354 yrlss hsmdlspot TL n HSL- lipolysis. but basal and of conditions control the ATGL- PKA-stimulated into insight supports to in limited offers enzyme lipolysis model the dependent allow This DAG would catalysing by LD hydrolysis. 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Fig. . https://doi.org/10.1017/S0029665109990279 TAG HSL yohtclmdlo aa n rti iaeA(K)siuae ioyi nhmnadipo- human in lipolysis (PKA)-stimulated A kinase protein and basal of model Hypothetical ATGL . IPaddress: G5 CGI58 CGI58 FA (94) (a) ti yohszdthat hypothesized is It . PLINA DAG 170.106.39.137 TGL AT FABP4 FA MAG , on Glycerol 08 Oct2021 at06:28:31 + FA HSL MGL ´ ar n .Langin D. and zaire lctyterl fAG nbsllipolysis basal in ATGL of role the plicitly rvd diinlinformation completes additional MGL provide HSL. glycerol. and by NEFA generating hydrolysed by further lipolysis a Generated are in hydrolysis. TAG DAG LD a PKA-stimulated CGI-58 to forms in and migrates it participate ATGL and or Together manner. 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ADAPT contract by HEPADIP, supported LSHM-CT-2005-018734, Project was (Integrated work Communities This Beaute the planned version. andYSL edited L. and final included additions D. the and and Figures. corrections suggested proposed the manuscript, manuscript, prepared the produced and B. of V. corrections draft interest. of first conflict the no declare authors The diabetes-related 2 type the and for obesity- avenue complications. and promising of metabolism a understanding between constitute tissue may adipose inflammation within talk cross 0 iakM 16)Atvto fa epinephrine-sensitive an of Activation (1964) MA Rizack 10. 2 rdisnG tafr ,NlsnNO Nilsson P, Stralfors G, Fredrikson 12. Immunological (1987) G Fredrikson & P Belfrage C, Holm 11. 4 to ,GnesnT,HnsnO Hansson TE, Gundersen K, Strom 14. 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