Trends in Cell Biology
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The adipocyte supersystem of insulin and cAMP signaling

Published:August 18, 2022DOI:


      • White adipose tissue lipid storage is promoted by insulin and antagonized by catecholamines that elevate cAMP to stimulate lipolysis and thermogenic adipocytes. Despite these antagonisms, whole body glucose tolerance is similarly enhanced by both insulin and chronic catecholamine stimulation of adipocytes.
      • We explore the concept that unanticipated convergences of the insulin and cAMP signaling networks in adipocytes contribute to common systemic outcomes. Indeed, the genes Lpin1, Ppargc1a, Gpr35, and Pck1, all known to promote metabolic health, appear to be similarly regulated by both signaling pathways in adipocytes.
      • Additionally, common signaling nodes for these hormones within adipocytes have recently been revealed, including mechanistic target of rapamycin complex (mTORC1), ATP citrate lyase (ACLY), and carbohydrate-responsive element-binding protein (ChREBP). Common stimulatory actions of insulin and cAMP in adipocytes also include glucose transport, glycogen synthesis, de novo lipogenesis, and secretion of adiponectin which enhances glucose tolerance.
      • How such common elements of adipocyte regulation are able to modulate other tissues such as liver and skeletal muscle that control whole body glucose and lipid homeostasis continues to be a key question in the field.
      Adipose tissue signals to brain, liver, and muscles to control whole body metabolism through secreted lipid and protein factors as well as neurotransmission, but the mechanisms involved are incompletely understood. Adipocytes sequester triglyceride (TG) in fed conditions stimulated by insulin, while in fasting catecholamines trigger TG hydrolysis, releasing glycerol and fatty acids (FAs). These antagonistic hormone actions result in part from insulin’s ability to inhibit cAMP levels generated through such G-protein-coupled receptors as catecholamine-activated β-adrenergic receptors. Consistent with these antagonistic signaling modes, acute actions of catecholamines cause insulin resistance. Yet, paradoxically, chronically activating adipocytes by catecholamines cause increased glucose tolerance, as does insulin. Recent results have helped to unravel this conundrum by revealing enhanced complexities of these hormones’ signaling networks, including identification of unexpected common signaling nodes between these canonically antagonistic hormones.


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        • White M.F.
        • Kahn C.R.
        Insulin action at a molecular level - 100 years of progress.
        Mol. Metab. 2021; 52101304
        • Zhou G.
        • et al.
        Multifaceted roles of cAMP signaling in the repair process of spinal cord injury and related combination treatments.
        Front. Mol. Neurosci. 2022; 15808510
        • Calamera G.
        • et al.
        Phosphodiesterases and compartmentation of cAMP and cGMP signaling in regulation of cardiac contractility in normal and failing hearts.
        Int. J. Mol. Sci. 2022; 23: 2145
        • Tengholm A.
        • Gylfe E.
        cAMP signalling in insulin and glucagon secretion.
        Diabetes Obes. Metab. 2017; 19: 42-53
        • Czech M.P.
        Insulin action and resistance in obesity and type 2 diabetes.
        Nat. Med. 2017; 23: 804-814
        • Klein S.
        • et al.
        Why does obesity cause diabetes?.
        Cell Metab. 2022; 34: 11-20
        • Lim K.
        • et al.
        Lipodistrophy: a paradigm for understanding the consequences of "overloading" adipose tissue.
        Physiol. Rev. 2021; 101: 907-993
        • Gavrilova O.
        • et al.
        Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice.
        J. Clin. Invest. 2000; 105: 271-278
        • Stanford K.I.
        • et al.
        Brown adipose tissue regulates glucose homeostasis and insulin sensitivity.
        J. Clin. Invest. 2013; 123: 215-223
        • Chai S.P.
        • Fong J.C.
        Synergistic induction of insulin resistance by endothelin-1 and cAMP in 3T3-L1 adipocytes.
        Biochim. Biophys. Acta. 2015; 1852: 2048-2055
        • Roach P.J.
        • et al.
        Glycogen and its metabolism: some new developments and old themes.
        Biochem. J. 2012; 441: 763-787
        • Bergman B.C.
        • et al.
        Effects of fasting on insulin action and glucose kinetics in lean and obese men and women.
        Am. J. Physiol. Endocrinol. Metab. 2007; 293: E1103-E1111
        • McKie G.L.
        • et al.
        Intermittent cold exposure improves glucose homeostasis despite exacerbating diet-induced obesity in mice housed at thermoneutrality.
        J. Physiol. 2022; 600: 829-845
        • Ravussin Y.
        • et al.
        Effect of intermittent cold exposure on brown fat activation, obesity, and energy homeostasis in mice.
        PLoS One. 2014; 9e85876
        • Grabner G.F.
        • et al.
        Lipolysis: cellular mechanisms for lipid mobilization from fat stores.
        Nat. Metab. 2021; 3: 1445-1465
        • Ikeda K.
        • Yamada T.
        UCP1 dependent and independent thermogenesis in brown and beige adipocytes.
        Front. Endocrinol. (Lausanne). 2020; 11: 498
        • Nedergaard J.
        • Cannon B.
        Brown adipose tissue as a heat-producing thermoeffector.
        Handb. Clin. Neurol. 2018; 156: 137-152
        • Ceddia R.P.
        • Collins S.
        A compendium of G-protein-coupled receptors and cyclic nucleotide regulation of adipose tissue metabolism and energy expenditure.
        Clin. Sci. (Lond.). 2020; 134: 473-512
        • Collins S.
        beta-Adrenergic receptors and adipose tissue metabolism: evolution of an old story.
        Annu. Rev. Physiol. 2022; 84: 1-16
        • Tan Y.Q.
        • et al.
        Epac, a positive or negative signaling molecule in cardiovascular diseases.
        Biomed. Pharmacother. 2022; 148112726
        • Villarroya J.
        • et al.
        New insights into the secretory functions of brown adipose tissue.
        J. Endocrinol. 2019; 243: R19-R27
        • Guillamat-Prats R.
        • et al.
        Endocannabinoid signalling in atherosclerosis and related metabolic complications.
        Thromb. Haemost. 2019; 119: 567-575
        • Zhao S.
        • et al.
        Adiponectin, leptin and cardiovascular disorders.
        Circ. Res. 2021; 128: 136-149
        • Funcke J.B.
        • Scherer P.E.
        Beyond adiponectin and leptin: adipose tissue-derived mediators of inter-organ communication.
        J. Lipid Res. 2019; 60: 1648-1684
        • Degerman E.
        • et al.
        From PDE3B to the regulation of energy homeostasis.
        Curr. Opin. Pharmacol. 2011; 11: 676-682
        • Mehran A.E.
        • et al.
        Hyperinsulinemia drives diet-induced obesity independently of brain insulin production.
        Cell Metab. 2012; 16: 723-737
        • Mowers J.
        • et al.
        Inflammation produces catecholamine resistance in obesity via activation of PDE3B by the protein kinases IKKepsilon and TBK1.
        Elife. 2013; 2e01119
        • Obregon M.J.
        Adipose tissues and thyroid hormones.
        Front. Physiol. 2014; 5: 479
        • Weiner J.
        • et al.
        Thyroid hormones and browning of adipose tissue.
        Mol. Cell. Endocrinol. 2017; 458: 156-159
        • Yau W.W.
        • Yen P.M.
        Thermogenesis in adipose tissue activated by thyroid hormone.
        Int. J. Mol. Sci. 2020; 21: 3020
        • Sentis S.C.
        • et al.
        Thyroid hormones in the regulation of brown adipose tissue thermogenesis.
        Endocr. Connect. 2021; 10: R106-R115
        • Carvalho S.D.
        • et al.
        Effects of hypothyroidism on brown adipose tissue adenylyl cyclase activity.
        Endocrinology. 1996; 137: 5519-5529
        • Rubio A.
        • et al.
        Effects of thyroid hormone on norepinephrine signaling in brown adipose tissue. I. Beta 1- and beta 2-adrenergic receptors and cyclic adenosine 3',5'-monophosphate generation.
        Endocrinology. 1995; 136: 3267-3276
        • Rubio A.
        • et al.
        Thyroid hormone and norepinephrine signaling in brown adipose tissue. II: differential effects of thyroid hormone on beta 3-adrenergic receptors in brown and white adipose tissue.
        Endocrinology. 1995; 136: 3277-3284
        • Guilherme A.
        • et al.
        Control of adipocyte thermogenesis and lipogenesis through beta3-adrenergic and thyroid hormone signal integration.
        Cell Rep. 2020; 31107598
        • Christoffolete M.A.
        • et al.
        Mice with targeted disruption of the Dio2 gene have cold-induced overexpression of the uncoupling protein 1 gene but fail to increase brown adipose tissue lipogenesis and adaptive thermogenesis.
        Diabetes. 2004; 53: 577-584
        • Bianco A.C.
        • et al.
        Paradigms of dynamic control of thyroid hormone signaling.
        Endocr. Rev. 2019; 40: 1000-1047
        • Mir N.
        • et al.
        Genomic and non-genomic actions of glucocorticoids on adipose tissue lipid metabolism.
        Int. J. Mol. Sci. 2021; 22: 8503
        • Shen Y.
        • et al.
        Adipocyte glucocorticoid receptor is important in lipolysis and insulin resistance due to exogenous steroids, but not insulin resistance caused by high fat feeding.
        Mol. Metab. 2017; 6: 1150-1160
        • Giroud M.
        • et al.
        HAND2 is a novel obesity-linked adipogenic transcription factor regulated by glucocorticoid signalling.
        Diabetologia. 2021; 64: 1850-1865
        • Ibanez C.F.
        Regulation of metabolic homeostasis by the TGF-beta superfamily receptor ALK7.
        FEBS J. 2021; (Published online June 26, 2021)
        • Guilherme A.
        • et al.
        Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes.
        Nat. Rev. Mol. Cell Biol. 2008; 9: 367-377
        • Andersson O.
        • et al.
        Growth/differentiation factor 3 signals through ALK7 and regulates accumulation of adipose tissue and diet-induced obesity.
        Proc. Natl. Acad. Sci. U. S. A. 2008; 105: 7252-7256
        • Balkow A.
        • et al.
        A novel crosstalk between Alk7 and cGMP signaling differentially regulates brown adipocyte function.
        Mol. Metab. 2015; 4: 576-583
        • Guo T.
        • et al.
        Adipocyte ALK7 links nutrient overload to catecholamine resistance in obesity.
        Elife. 2014; 3e03245
        • Yogosawa S.
        • et al.
        Activin receptor-like kinase 7 suppresses lipolysis to accumulate fat in obesity through downregulation of peroxisome proliferator-activated receptor gamma and C/EBPalpha.
        Diabetes. 2013; 62: 115-123
        • Yogosawa S.
        • Izumi T.
        Roles of activin receptor-like kinase 7 signaling and its target, peroxisome proliferator-activated receptor gamma, in lean and obese adipocytes.
        Adipocyte. 2013; 2: 246-250
        • Valentine J.M.
        • et al.
        beta3-Adrenergic receptor downregulation leads to adipocyte catecholamine resistance in obesity.
        J. Clin. Invest. 2022; 132e153357
        • Koren S.
        • et al.
        The role of mouse Akt2 in insulin-dependent suppression of adipocyte lipolysis in vivo.
        Diabetologia. 2015; 58: 1063-1070
        • DiPilato L.M.
        • et al.
        The role of PDE3B phosphorylation in the inhibition of lipolysis by insulin.
        Mol. Cell. Biol. 2015; 35: 2752-2760
        • Gabbay R.A.
        • Lardy H.A.
        The antilipolytic effect of insulin does not require adenylate cyclase or phosphodiesterase action.
        FEBS Lett. 1985; 179: 7-11
        • Sancar G.
        • et al.
        FGF1 and insulin control lipolysis by convergent pathways.
        Cell Metab. 2022; 34: 171-183 e6
        • Stockli J.
        • et al.
        ABHD15 regulates adipose tissue lipolysis and hepatic lipid accumulation.
        Mol. Metab. 2019; 25: 83-94
        • Rebrin K.
        • et al.
        Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs.
        J. Clin. Invest. 1996; 98: 741-749
        • Perry R.J.
        • et al.
        Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes.
        Cell. 2015; 160: 745-758
        • Titchenell P.M.
        • et al.
        Hepatic insulin signalling is dispensable for suppression of glucose output by insulin in vivo.
        Nat. Commun. 2015; 6: 7078
        • Mauvais-Jarvis F.
        • et al.
        Reduced expression of the murine p85alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes.
        J. Clin. Invest. 2002; 109: 141-149
        • Morley T.S.
        • et al.
        Selective enhancement of insulin sensitivity in the mature adipocyte is sufficient for systemic metabolic improvements.
        Nat. Commun. 2015; 6: 7906
        • Schoiswohl G.
        • et al.
        Impact of reduced ATGL-mediated adipocyte lipolysis on obesity-associated insulin resistance and inflammation in male mice.
        Endocrinology. 2015; 156: 3610-3624
        • Shearin A.L.
        • et al.
        Lack of AKT in adipocytes causes severe lipodystrophy.
        Mol. Metab. 2016; 5: 472-479
        • Herman M.A.
        • et al.
        A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism.
        Nature. 2012; 484: 333-338
        • Iwen K.A.
        • et al.
        Cold-induced brown adipose tissue activity alters plasma fatty acids and improves glucose metabolism in men.
        J. Clin. Endocrinol. Metab. 2017; 102: 4226-4234
        • Xiao C.
        • et al.
        Anti-obesity and metabolic efficacy of the beta3-adrenergic agonist, CL316243, in mice at thermoneutrality compared to 22 degrees C.
        Obesity (Silver Spring). 2015; 23: 1450-1459
        • Michel L.Y.M.
        • et al.
        The beta3 adrenergic receptor in healthy and pathological cardiovascular tissues.
        Cells. 2020; 9: 2584
        • Lowell B.B.
        • Flier J.S.
        Brown adipose tissue, beta 3-adrenergic receptors, and obesity.
        Annu. Rev. Med. 1997; 48: 307-316
        • Cero C.
        • et al.
        beta3-Adrenergic receptors regulate human brown/beige adipocyte lipolysis and thermogenesis.
        JCI Insight. 2021; 6e139160
        • O'Mara A.E.
        • et al.
        Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity.
        J. Clin. Invest. 2020; 130: 2209-2219
        • Cypess A.M.
        Reassessing human adipose tissue.
        N. Engl. J. Med. 2022; 386: 768-779
        • Cohen P.
        • et al.
        Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch.
        Cell. 2014; 156: 304-316
        • Chung Y.W.
        • et al.
        White to beige conversion in PDE3B KO adipose tissue through activation of AMPK signaling and mitochondrial function.
        Sci. Rep. 2017; 7: 40445
        • Degirmenci U.
        • et al.
        Silencing an insulin-induced lncRNA, LncASIR, impairs the transcriptional response to insulin signalling in adipocytes.
        Sci. Rep. 2019; 9: 5608
        • Abu-Odeh M.
        • et al.
        FGF21 promotes thermogenic gene expression as an autocrine factor in adipocytes.
        Cell Rep. 2021; 35109331
        • Phan J.
        • Reue K.
        Lipin, a lipodystrophy and obesity gene.
        Cell Metab. 2005; 1: 73-83
        • Franckhauser S.
        • et al.
        Increased fatty acid re-esterification by PEPCK overexpression in adipose tissue leads to obesity without insulin resistance.
        Diabetes. 2002; 51: 624-630
        • Kleiner S.
        • et al.
        Development of insulin resistance in mice lacking PGC-1alpha in adipose tissues.
        Proc. Natl. Acad. Sci. U. S. A. 2012; 109: 9635-9640
        • Puigserver P.
        • et al.
        A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis.
        Cell. 1998; 92: 829-839
        • Agudelo L.Z.
        • et al.
        Kynurenic acid and Gpr35 regulate adipose tissue energy homeostasis and inflammation.
        Cell Metab. 2018; 27: 378-392 e5
        • Liu D.
        • et al.
        Activation of mTORC1 is essential for beta-adrenergic stimulation of adipose browning.
        J. Clin. Invest. 2016; 126: 1704-1716
        • Liu D.
        • et al.
        Cardiac natriuretic peptides promote adipose 'browning' through mTOR complex-1.
        Mol. Metab. 2018; 9: 192-198
        • Olsen J.M.
        • et al.
        beta3-Adrenergically induced glucose uptake in brown adipose tissue is independent of UCP1 presence or activity: mediation through the mTOR pathway.
        Mol. Metab. 2017; 6: 611-619
        • Ikeda K.
        • et al.
        UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis.
        Nat. Med. 2017; 23: 1454-1465
        • Chypre M.
        • et al.
        ATP-citrate lyase: a mini-review.
        Biochem. Biophys. Res. Commun. 2012; 422: 1-4
        • Berwick D.C.
        • et al.
        The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes.
        J. Biol. Chem. 2002; 277: 33895-33900
        • Potapova I.A.
        • et al.
        Phosphorylation of recombinant human ATP:citrate lyase by cAMP-dependent protein kinase abolishes homotropic allosteric regulation of the enzyme by citrate and increases the enzyme activity. Allosteric activation of ATP:citrate lyase by phosphorylated sugars.
        Biochemistry. 2000; 39: 1169-1179
        • Pierce M.W.
        • et al.
        ATP-citrate lyase. Structure of a tryptic peptide containing the phosphorylation site directed by glucagon and the cAMP-dependent protein kinase.
        J. Biol. Chem. 1981; 256: 8867-8870
        • Pierce M.W.
        • et al.
        The insulin-directed phosphorylation site on ATP-citrate lyase is identical with the site phosphorylated by the cAMP-dependent protein kinase in vitro.
        J. Biol. Chem. 1982; 257: 10681-10686
        • Fernandez S.
        • et al.
        Adipocyte ACLY facilitates dietary carbohydrate handling to maintain metabolic homeostasis in females.
        Cell Rep. 2019; 27: 2772-2784 e6
        • Abdul-Wahed A.
        • et al.
        Sweet sixteenth for ChREBP: established roles and future goals.
        Cell Metab. 2017; 26: 324-341
        • Ortega-Prieto P.
        • Postic C.
        Carbohydrate sensing through the transcription factor ChREBP.
        Front. Genet. 2019; 10: 472
        • Martinez Calejman C.
        • et al.
        mTORC2-AKT signaling to ATP-citrate lyase drives brown adipogenesis and de novo lipogenesis.
        Nat. Commun. 2020; 11: 575
        • Czech M.P.
        Mechanisms of insulin resistance related to white, beige, and brown adipocytes.
        Mol. Metab. 2020; 34: 27-42
        • Albert V.
        • et al.
        mTORC2 sustains thermogenesis via Akt-induced glucose uptake and glycolysis in brown adipose tissue.
        EMBO Mol. Med. 2016; 8: 232-246
        • Olsen J.M.
        • et al.
        Glucose uptake in brown fat cells is dependent on mTOR complex 2-promoted GLUT1 translocation.
        J. Cell Biol. 2014; 207: 365-374
        • Keinan O.
        • et al.
        Glycogen metabolism links glucose homeostasis to thermogenesis in adipocytes.
        Nature. 2021; 599: 296-301
        • Heine M.
        • et al.
        Lipolysis triggers a systemic insulin response essential for efficient energy replenishment of activated brown adipose tissue in mice.
        Cell Metab. 2018; 28: 644-655 e4
        • Jung S.M.
        • et al.
        In vivo isotope tracing reveals the versatility of glucose as a brown adipose tissue substrate.
        Cell Rep. 2021; 36109459
        • Zingaretti M.C.
        • et al.
        The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue.
        FASEB J. 2009; 23: 3113-3120
        • Leiria L.O.
        • et al.
        12-Lipoxygenase regulates cold adaptation and glucose metabolism by producing the omega-3 lipid 12-HEPE from brown fat.
        Cell Metab. 2019; 30: 768-783 e7
        • Stanford K.I.
        • et al.
        12,13-diHOME: an exercise-induced lipokine that increases skeletal muscle fatty acid uptake.
        Cell Metab. 2018; 27: 1111-1120 e3
        • Nagatake T.
        • et al.
        12-Hydroxyeicosapentaenoic acid inhibits foam cell formation and ameliorates high-fat diet-induced pathology of atherosclerosis in mice.
        Sci. Rep. 2021; 11: 10426
        • Pinckard K.M.
        • et al.
        A novel endocrine role for the BAT-released lipokine 12,13-diHOME to mediate cardiac function.
        Circulation. 2021; 143: 145-159
        • Hajri T.
        • et al.
        Regulation of adiponectin production by insulin: interactions with tumor necrosis factor-alpha and interleukin-6.
        Am. J. Physiol. Endocrinol. Metab. 2011; 300: E350-E360
        • Musovic S.
        • Olofsson C.S.
        Adrenergic stimulation of adiponectin secretion in visceral mouse adipocytes is blunted in high-fat diet induced obesity.
        Sci. Rep. 2019; 9: 10680
        • Olzmann J.A.
        • Carvalho P.
        Dynamics and functions of lipid droplets.
        Nat. Rev. Mol. Cell Biol. 2019; 20: 137-155
        • Boutant M.
        • et al.
        Mfn2 is critical for brown adipose tissue thermogenic function.
        EMBO J. 2017; 36: 1543-1558
        • Xu N.
        • et al.
        The FATP1-DGAT2 complex facilitates lipid droplet expansion at the ER-lipid droplet interface.
        J. Cell Biol. 2012; 198: 895-911
        • Puri V.
        • et al.
        Cidea is associated with lipid droplets and insulin sensitivity in humans.
        Proc. Natl. Acad. Sci. U. S. A. 2008; 105: 7833-7838
        • Nishino N.
        • et al.
        FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets.
        J. Clin. Invest. 2008; 118: 2808-2821
        • Rubio-Cabezas O.
        • et al.
        Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC.
        EMBO Mol. Med. 2009; 1: 280-287
        • Xu S.
        • et al.
        Lipid droplet proteins and metabolic diseases.
        Biochim. Biophys. Acta Mol. Basis Dis. 2018; : 1968-1983
        • Smith G.I.
        • et al.
        Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease.
        J. Clin. Invest. 2020; 130: 1453-1460
        • Czech M.P.
        • et al.
        Insulin signalling mechanisms for triacylglycerol storage.
        Diabetologia. 2013; 56: 949-964
        • Wallace M.
        • Metallo C.M.
        Tracing insights into de novo lipogenesis in liver and adipose tissues.
        Semin. Cell Dev. Biol. 2020; 108: 65-71
        • Song Z.
        • et al.
        Regulation and metabolic significance of de novo lipogenesis in adipose tissues.
        Nutrients. 2018; 10: 1383
        • Cao H.
        • et al.
        Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism.
        Cell. 2008; 134: 933-944
        • Yore M.M.
        • et al.
        Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects.
        Cell. 2014; 159: 318-332
        • Lodhi I.J.
        • et al.
        Inhibiting adipose tissue lipogenesis reprograms thermogenesis and PPARgamma activation to decrease diet-induced obesity.
        Cell Metab. 2012; 16: 189-201
        • Grunt T.W.
        • et al.
        Membrane disruption, but not metabolic rewiring, is the key mechanism of anticancer-action of FASN-inhibitors: a multi-omics analysis in ovarian cancer.
        Sci. Rep. 2020; 10: 14877


      Activin A receptor type 1C (ALK7)
      a type I receptor for the TGFβ family of signaling molecules. In adipocytes, activation of ALK7 reduces β-adrenergic receptor-mediated signaling and lipolysis.
      Adipose triglyceride lipase (ATGL)
      an enzyme that catalyzes hydrolysis of triacylglycerols to diacylglycerol and FA.
      ATP citrate lyase (ACLY)
      an enzyme that initiates the de novo lipogenesis pathway by converting citrate to acetyl-CoA.
      cAMP response element-binding protein (CREB)
      a transcriptional regulator that modulates the transcription of genes with cAMP responsive elements in their promoters.
      Carbohydrate response element binding protein (ChREBP)
      glycolytic metabolite activated transcription factors (ChREBPα and ChREBPβ) that regulate glycolytic and lipogenic pathways.
      hormones that are produced in nerve tissues and adrenal glands and function as neurotransmitters.
      Chow diet
      a standard control diet for rodents, generally providing only 7–12% of the total energy from fat.
      cAMP signaling pathway
      a G-protein-coupled receptor-triggered signaling cascade in cell communication, which plays a central role in lipolysis and thermogenesis in adipocytes.
      De novo lipogenesis (DNL)
      a pathway that converts carbons from nutrients into FAs, which are precursors for synthesizing TGs or other lipids.
      Deiodinase (Dio2)
      an enzyme to convert thyroid hormone from thyroxine (T4) to active form triiodothyronine (T3).
      Fatty acid synthase (FASN)
      the last enzyme in DNL, catalyzing synthesis of palmitic acid.
      a subunit of the heterotrimeric G protein Gs that stimulates the cAMP-dependent pathway by activating adenylyl cyclase.
      Histone acetylation
      a critical epigenetic modification that changes chromatin architecture and regulates gene expression by modulating chromatin structure.
      Hormone-sensitive lipase (HSL)
      a rate-limiting enzyme, hydrolyzing diacylglycerol to monoacylglycerol and FAs.
      syndromes with abnormal distribution of fat due to the loss of functional adipose tissue depots.
      a process which breaks down triacylglycerols to glycerol and free FAs.
      Mechanistic target of rapamycin complex 1 (mTORC1)
      a protein complex that functions as a nutrient/energy/redox sensor and controls protein and lipid synthesis.
      Mechanistic target of rapamycin complex 2 (mTORC2)
      a rapamycin-insensitive protein complex formed by serine/threonine kinase mTOR that regulates cell proliferation and survival, cell migration and cytoskeletal remodeling.
      Phosphodiesterases (PDEs)
      enzymes that catalyze degradation of cyclic nucleotides cAMP and cGMP to AMP and GMP, respectively, reducing cAMP and cGMP signaling.
      Protein kinase A (PKA)
      a family of enzymes whose activity is dependent on cellular levels of cyclic AMP (cAMP).
      Protein kinase B (Akt)
      a group of three insulin-activated serine/threonine-specific protein kinases that play key roles in multiple cellular processes.
      Uncoupling protein 1 (UCP1)
      a unique mitochondrial inner-membrane uncoupling protein devoted to heat production (thermogenesis) in beige and brown adipocytes.
      Tumor necrosis factor α (TNF-α)
      an inflammatory cytokine produced by macrophages/monocytes during acute inflammation, leading to necrosis or apoptosis.