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Volume 50 Issue 5
May  2023
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Article Contents

Peripheral and central control of obesity by primary cilia

doi: 10.1016/j.jgg.2022.12.006
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This work was supported by the National Natural Science Foundation of China (32100948, 32100614, 31991193) and Natural Science Foundation of Shandong Province (ZR2021QC069).

  • Received Date: 2022-08-22
  • Accepted Date: 2022-12-30
  • Rev Recd Date: 2022-12-29
  • Publish Date: 2023-01-09
  • Primary cilia are hair-like structures that protrude from the cell surface. They are capable of sensing external cues and conveying a vast array of signals into cells to regulate a variety of physiological activities. Mutations in cilium-associated genes are linked to a group of diseases with overlapping clinical manifestations, collectively known as ciliopathies. A significant proportion of human ciliopathy cases are accompanied by metabolic disorders such as obesity and type 2 diabetes. Nevertheless, the mechanisms through which dysfunction of primary cilia contributes to obesity are complex. In this review, we present an overview of primary cilia and highlight obesity-related ciliopathies. We also discuss the potential role of primary cilia in peripheral organs, with a focus on adipose tissues. In addition, we emphasize the significance of primary cilia in the central regulation of obesity, especially the involvement of ciliary signaling in the hypothalamic control of feeding behavior. This review therefore proposes a framework of both peripheral and central regulation of obesity by primary cilia, which may benefit further exploration of the ciliary role in metabolic regulation.
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  • [1]
    Acs, P., Bauer, P.O., Mayer, B., Bera, T., Macallister, R., Mezey, E., Pastan, I., 2015. A novel form of ciliopathy underlies hyperphagia and obesity in ankrd26 knockout mice. Brain Struct. Funct. 220, 1511-1528.
    [2]
    Ait-Lounis, A., Baas, D., Barras, E., Benadiba, C., Charollais, A., Nlend Nlend, R., Liegeois, D., Meda, P., Durand, B., Reith, W., 2007. Novel function of the ciliogenic transcription factor rfx3 in development of the endocrine pancreas. Diabetes 56, 950-959.
    [3]
    Aksanov, O., Green, P., Birk, R.Z., 2014. Bbs4 directly affects proliferation and differentiation of adipocytes. Cell. Mol. Life Sci. 71, 3381-3392.
    [4]
    Anvarian, Z., Mykytyn, K., Mukhopadhyay, S., Pedersen, L.B.,Christensen, S.T., 2019. Cellular signalling by primary cilia in development, organ function and disease. Nat. Rev. Nephrol. 15, 199-219.
    [5]
    Arrighi, N., Lypovetska, K., Moratal, C., Giorgetti-Peraldi, S., Dechesne, C.A., Dani, C.,Peraldi, P., 2017. The primary cilium is necessary for the differentiation and the maintenance of human adipose progenitors into myofibroblasts. Sci. Rep. 7, 15248.
    [6]
    Benzinou, M., Walley, A., Lobbens, S., Charles, M.A., Jouret, B., Fumeron, F., Balkau, B., Meyre, D.,Froguel, P., 2006. Bardet-biedl syndrome gene variants are associated with both childhood and adult common obesity in French caucasians. Diabetes 55, 2876-2882.
    [7]
    Berbari, N.F., Lewis, J.S., Bishop, G.A., Askwith, C.C.,Mykytyn, K., 2008. Bardet-biedl syndrome proteins are required for the localization of g protein-coupled receptors to primary cilia. Proc. Natl. Acad. Sci. U.S.A. 105, 4242-4246.
    [8]
    Berbari, N.F., O'Connor, A.K., Haycraft, C.J.,Yoder, B.K., 2009. The primary cilium as a complex signaling center. Curr. Biol. 19, R526-R535.
    [9]
    Berbari, N.F., Pasek, R.C., Malarkey, E.B., Yazdi, S.M., McNair, A.D., Lewis, W.R., Nagy, T.R., Kesterson, R.A.,Yoder, B.K., 2013. Leptin resistance is a secondary consequence of the obesity in ciliopathy mutant mice. Proc. Natl. Acad. Sci. U.S.A. 110, 7796-7801.
    [10]
    Boehlke, C., Bashkurov, M., Buescher, A., Krick, T., John, A.K., Nitschke, R., Walz, G.,Kuehn, E.W., 2010. Differential role of rab proteins in ciliary trafficking: rab23 regulates smoothened levels. J. Cell Sci. 123, 1460-1467.
    [11]
    Braun, D.A.,Hildebrandt, F., 2017. Ciliopathies. Cold Spring Harbor Perspect. Biol. 9.
    [12]
    Cano, D.A., Sekine, S.,Hebrok, M., 2006. Primary cilia deletion in pancreatic epithelial cells results in cyst formation and pancreatitis. Gastroenterology 131, 1856-1869.
    [13]
    Chouchani, E.T.,Kajimura, S., 2019. Metabolic adaptation and maladaptation in adipose tissue. Nat. Metab. 1, 189-200.
    [14]
    Conde, J., Scotece, M., Gomez, R., Lopez, V., Gomez-Reino, J.J., Lago, F.,Gualillo, O., 2011. Adipokines: biofactors from white adipose tissue. A complex hub among inflammation, metabolism, and immunity. Biofactors 37, 413-420.
    [15]
    Cook, L.B., Ophardt, H.D., Shen, R., Pratt, B.H.,Galbier, L.A., 2021. Transcriptome analysis of ciliary-dependent mch signaling in differentiating 3t3-l1 pre-adipocytes. Sci. Rep. 11, 4880.
    [16]
    Corbit, K.C., Shyer, A.E., Dowdle, W.E., Gaulden, J., Singla, V., Chen, M.H., Chuang, P.T.,Reiter, J.F., 2008. Kif3a constrains beta-catenin-dependent wnt signalling through dual ciliary and non-ciliary mechanisms. Nat. Cell Biol. 10, 70-76.
    [17]
    Dalbay, M.T., Thorpe, S.D., Connelly, J.T., Chapple, J.P.,Knight, M.M., 2015. Adipogenic differentiation of hmscs is mediated by recruitment of igf-1r onto the primary cilium associated with cilia elongation. Stem Cell. 33, 1952-1961.
    [18]
    Davenport, J.R., Watts, A.J., Roper, V.C., Croyle, M.J., van Groen, T., Wyss, J.M., Nagy, T.R., Kesterson, R.A.,Yoder, B.K., 2007. Disruption of intraflagellar transport in adult mice leads to obesity and slow-onset cystic kidney disease. Curr. Biol. 17, 1586-1594.
    [19]
    Dyson, J.M., Conduit, S.E., Feeney, S.J., Hakim, S., DiTommaso, T., Fulcher, A.J., Sriratana, A., Ramm, G., Horan, K.A., Gurung, R., et al., 2017. Inpp5e regulates phosphoinositide-dependent cilia transition zone function. J. Cell Biol. 216, 247-263.
    [20]
    Favaretto, F., Milan, G., Collin, G.B., Marshall, J.D., Stasi, F., Maffei, P., Vettor, R.,Naggert, J.K., 2014. Glut4 defects in adipose tissue are early signs of metabolic alterations in alms1gt/gt, a mouse model for obesity and insulin resistance. PLoS One 9, e109540.
    [21]
    Forcioli-Conti, N., Lacas-Gervais, S., Dani, C.,Peraldi, P., 2015. The primary cilium undergoes dynamic size modifications during adipocyte differentiation of human adipose stem cells. Biochem. Biophys. Res. Commun. 458, 117-122.
    [22]
    Friedman, J.M., 2019. Leptin and the endocrine control of energy balance. Nat. Metab. 1, 754-764.
    [23]
    Garcia, G., 3rd, Raleigh, D.R.,Reiter, J.F., 2018. How the ciliary membrane is organized inside-out to communicate outside-in. Curr. Biol. 28, R421-R434.
    [24]
    Garcia-Gonzalo, F.R., Phua, S.C., Roberson, E.C., Garcia, G., 3rd, Abedin, M., Schurmans, S., Inoue, T.,Reiter, J.F., 2015. Phosphoinositides regulate ciliary protein trafficking to modulate hedgehog signaling. Dev. Cell 34, 400-409.
    [25]
    Garfield, A.S., Li, C., Madara, J.C., Shah, B.P., Webber, E., Steger, J.S., Campbell, J.N., Gavrilova, O., Lee, C.E., Olson, D.P., et al., 2015. A neural basis for melanocortin-4 receptor-regulated appetite. Nat. Neurosci. 18, 863-871.
    [26]
    Gerdes, J.M., Christou-Savina, S., Xiong, Y., Moede, T., Moruzzi, N., Karlsson-Edlund, P., Leibiger, B., Leibiger, I.B., Ostenson, C.G., Beales, P.L., et al., 2014. Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents. Nat. Commun. 5, 5308.
    [27]
    Ghaben, A.L.,Scherer, P.E., 2019. Adipogenesis and metabolic health. Nat. Rev. Mol. Cell Biol. 20, 242-258.
    [28]
    Gohlke, S., Mancini, C., Garcia-Carrizo, F.,Schulz, T.J., 2021. Loss of the ciliary gene bbs4 results in defective thermogenesis due to metabolic inefficiency and impaired lipid metabolism. Faseb. J. 35, e21966.
    [29]
    Hampshire, D.J., Ayub, M., Springell, K., Roberts, E., Jafri, H., Rashid, Y., Bond, J., Riley, J.H.,Woods, C.G., 2006. Morm syndrome (mental retardation, truncal obesity, retinal dystrophy and micropenis), a new autosomal recessive disorder, links to 9q34. Eur. J. Hum. Genet. 14, 543-548.
    [30]
    Han, Y.M., Kang, G.M., Byun, K., Ko, H.W., Kim, J., Shin, M.S., Kim, H.K., Gil, S.Y., Yu, J.H., Lee, B., et al., 2014. Leptin-promoted cilia assembly is critical for normal energy balance. J. Clin. Invest. 124, 2193-2197.
    [31]
    Hao, K., Chen, Y., Yan, X.,Zhu, X., 2021. Cilia locally synthesize proteins to sustain their ultrastructure and functions. Nat. Commun. 12, 6971.
    [32]
    Hearn, T., 2019. Alms1 and alstrom syndrome: a recessive form of metabolic, neurosensory and cardiac deficits. J. Mol. Med (Berl) 97, 1-17.
    [33]
    Heydet, D., Chen, L.X., Larter, C.Z., Inglis, C., Silverman, M.A., Farrell, G.C.,Leroux, M.R., 2013. A truncating mutation of alms1 reduces the number of hypothalamic neuronal cilia in obese mice. Dev. Neurobiol. 73, 1-13.
    [34]
    Hilgendorf, K.I., Johnson, C.T., Mezger, A., Rice, S.L., Norris, A.M., Demeter, J., Greenleaf, W.J., Reiter, J.F., Kopinke, D., Jackson, P.K., 2019. Omega-3 fatty acids activate ciliary ffar4 to control adipogenesis. Cell 179, 1289-1305 e1221.
    [35]
    Huang-Doran, I.,Semple, R.K., 2010. Knockdown of the alstrom syndrome-associated gene alms1 in 3t3-l1 preadipocytes impairs adipogenesis but has no effect on cell-autonomous insulin action. Int. J. Obes. 34, 1554-1558.
    [36]
    Jacoby, M., Cox, J.J., Gayral, S., Hampshire, D.J., Ayub, M., Blockmans, M., Pernot, E., Kisseleva, M.V., Compere, P., Schiffmann, S.N., et al., 2009. Inpp5e mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse. Nat. Genet. 41, 1027-1031.
    [37]
    Jais, A.,Bruning, J.C., 2017. Hypothalamic inflammation in obesity and metabolic disease. J. Clin. Invest. 127, 24-32.
    [38]
    Jais, A., Paeger, L., Sotelo-Hitschfeld, T., Bremser, S., Prinzensteiner, M., Klemm, P., Mykytiuk, V., Widdershooven, P.J.M., Vesting, A.J., Grzelka, K., et al., 2020. Pnoc(arc) neurons promote hyperphagia and obesity upon high-fat-diet feeding. Neuron 106, 1009-1025 e1010.
    [39]
    Jenkins, D., Baynam, G., De Catte, L., Elcioglu, N., Gabbett, M.T., Hudgins, L., Hurst, J.A., Jehee, F.S., Oley, C.,Wilkie, A.O., 2011. Carpenter syndrome: extended rab23 mutation spectrum and analysis of nonsense-mediated mrna decay. Hum. Mutat. 32, E2069-E2078.
    [40]
    Jiang, J., Promchan, K., Jiang, H., Awasthi, P., Marshall, H., Harned, A.,Natarajan, V., 2016. Depletion of bbs protein lztfl1 affects growth and causes retinal degeneration in mice. J. Genet. Genomics 43, 381-391.
    [41]
    Jin, H., White, S.R., Shida, T., Schulz, S., Aguiar, M., Gygi, S.P., Bazan, J.F.,Nachury, M.V., 2010. The conserved bardet-biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia. Cell 141, 1208-1219.
    [42]
    Kang, H.S., Kim, Y.S., ZeRuth, G., Beak, J.Y., Gerrish, K., Kilic, G., Sosa-Pineda, B., Jensen, J., Pierreux, C.E., Lemaigre, F.P., et al., 2009. Transcription factor glis3, a novel critical player in the regulation of pancreatic beta-cell development and insulin gene expression. Mol. Cell Biol. 29, 6366-6379.
    [43]
    Kang, S., 2021. Adipose tissue malfunction drives metabolic dysfunction in alstrom syndrome. Diabetes 70, 323-325.
    [44]
    Khan, S., Lin, S., Harlalka, G.V., Ullah, A., Shah, K., Khalid, S., Mehmood, S., Hassan, M.J., Ahmad, W., Self, J.E., et al., 2019. Bbs5 and inpp5e mutations associated with ciliopathy disorders in families from Pakistan. Ann. Hum. Genet. 83, 477-482.
    [45]
    Kopinke, D., Roberson, E.C.,Reiter, J.F., 2017. Ciliary hedgehog signaling restricts injury-induced adipogenesis. Cell 170, 340-351 e312.
    [46]
    Korostishevsky, M., Cohen, Z., Malkin, I., Ermakov, S., Yarenchuk, O.,Livshits, G., 2010. Morphological and biochemical features of obesity are associated with mineralization genes' polymorphisms. Int. J. Obes. 34, 1308-1318.
    [47]
    Lee, C.H., Song, D.K., Park, C.B., Choi, J., Kang, G.M., Shin, S.H., Kwon, I., Park, S., Kim, S., Kim, J.Y., et al., 2020. Primary cilia mediate early life programming of adiposity through lysosomal regulation in the developing mouse hypothalamus. Nat. Commun. 11, 5772.
    [48]
    Leibowitz, S.F., Hammer, N.J.,Chang, K., 1981. Hypothalamic paraventricular nucleus lesions produce overeating and obesity in the rat. Physiol. Behav. 27, 1031-1040.
    [49]
    Li, M.M., Madara, J.C., Steger, J.S., Krashes, M.J., Balthasar, N., Campbell, J.N., Resch, J.M., Conley, N.J., Garfield, A.S.,Lowell, B.B., 2019. The paraventricular hypothalamus regulates satiety and prevents obesity via two genetically distinct circuits. Neuron 102, 653-667 e656.
    [50]
    Li, S., Wan, K.Y., Chen, W., Tao, H., Liang, X.,Pan, J., 2020. Functional exploration of heterotrimeric kinesin-ii in ift and ciliary length control in chlamydomonas. Elife 9.
    [51]
    Li, Y.,Hu, J., 2011. Small gtpases and cilia. Protein Cell 2, 13-25.
    [52]
    Liao, X., Zhou, H.,Deng, T., 2022. The composition, function, and regulation of adipose stem and progenitor cells. J. Genet. Genomics 49, 308-315.
    [53]
    Liu, K., Jin, X., Zhang, X., Lian, H.,Ye, J., 2022. The mechanisms of nucleotide actions in insulin resistance. J. Genet. Genomics 49, 299-307.
    [54]
    Liu, L., Zhang, M., Xia, Z., Xu, P., Chen, L.,Xu, T., 2011. Caenorhabditis elegans ciliary protein nphp-8, the homologue of human rpgrip1l, is required for ciliogenesis and chemosensation. Biochem. Biophys. Res. Commun. 410, 626-631.
    [55]
    Loktev, A.V.,Jackson, P.K., 2013. Neuropeptide y family receptors traffic via the bardet-biedl syndrome pathway to signal in neuronal primary cilia. Cell Rep. 5, 1316-1329.
    [56]
    Lonn, M., Mehlig, K., Bengtsson, C.,Lissner, L., 2010. Adipocyte size predicts incidence of type 2 diabetes in women. Faseb. J. 24, 326-331.
    [57]
    Malicki, J.J.,Johnson, C.A., 2017. The cilium: cellular antenna and central processing unit. Trends Cell Biol. 27, 126-140.
    [58]
    Marion, V., Mockel, A., De Melo, C., Obringer, C., Claussmann, A., Simon, A., Messaddeq, N., Durand, M., Dupuis, L., Loeffler, J.P., et al., 2012. Bbs-induced ciliary defect enhances adipogenesis, causing paradoxical higher-insulin sensitivity, glucose usage, and decreased inflammatory response. Cell Metabol. 16, 363-377.
    [59]
    Marion, V., Stoetzel, C., Schlicht, D., Messaddeq, N., Koch, M., Flori, E., Danse, J.M., Mandel, J.L.,Dollfus, H., 2009. Transient ciliogenesis involving bardet-biedl syndrome proteins is a fundamental characteristic of adipogenic differentiation. Proc. Natl. Acad. Sci. U.S.A. 106, 1820-1825.
    [60]
    Morton, G.J., Cummings, D.E., Baskin, D.G., Barsh, G.S.,Schwartz, M.W., 2006. Central nervous system control of food intake and body weight. Nature 443, 289-295.
    [61]
    Morton, G.J., Meek, T.H.,Schwartz, M.W., 2014. Neurobiology of food intake in health and disease. Nat. Rev. Neurosci. 15, 367-378.
    [62]
    Nishimura, Y., Kasahara, K., Shiromizu, T., Watanabe, M.,Inagaki, M., 2019. Primary cilia as signaling hubs in health and disease. Adv. Sci. 6, 1801138.
    [63]
    Oh, D.Y., Talukdar, S., Bae, E.J., Imamura, T., Morinaga, H., Fan, W., Li, P., Lu, W.J., Watkins, S.M.,Olefsky, J.M., 2010. Gpr120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142, 687-698.
    [64]
    Oh, E.C., Vasanth, S.,Katsanis, N., 2015. Metabolic regulation and energy homeostasis through the primary cilium. Cell Metabol. 21, 21-31.
    [65]
    Pala, R., Jamal, M., Alshammari, Q.,Nauli, S.M., 2018. The roles of primary cilia in cardiovascular diseases. Cells 7.
    [66]
    Phua, S.C., Chiba, S., Suzuki, M., Su, E., Roberson, E.C., Pusapati, G.V., Schurmans, S., Setou, M., Rohatgi, R., Reiter, J.F., et al., 2017. Dynamic remodeling of membrane composition drives cell cycle through primary cilia excision. Cell 168, 264-279 e215.
    [67]
    Pospisilik, J.A., Schramek, D., Schnidar, H., Cronin, S.J., Nehme, N.T., Zhang, X., Knauf, C., Cani, P.D., Aumayr, K., Todoric, J., et al., 2010. Drosophila genome-wide obesity screen reveals hedgehog as a determinant of brown versus white adipose cell fate. Cell 140, 148-160.
    [68]
    Rahmouni, K., Fath, M.A., Seo, S., Thedens, D.R., Berry, C.J., Weiss, R., Nishimura, D.Y.,Sheffield, V.C., 2008. Leptin resistance contributes to obesity and hypertension in mouse models of bardet-biedl syndrome. J. Clin. Invest. 118, 1458-1467.
    [69]
    Ran, J., Liu, M., Feng, J., Li, H., Ma, H., Song, T., Cao, Y., Zhou, P., Wu, Y., Yang, Y., et al., 2020. Ask1-mediated phosphorylation blocks hdac6 ubiquitination and degradation to drive the disassembly of photoreceptor connecting cilia. Dev. Cell 53, 287-299 e285.
    [70]
    Ran, J., Zhang, Y., Zhang, S., Li, H., Zhang, L., Li, Q., Qin, J., Li, D., Sun, L., Xie, S., et al., 2022. Targeting the hdac6-cilium axis ameliorates the pathological changes associated with retinopathy of prematurity. Adv. Sci., e2105365.
    [71]
    Ran, J.,Zhou, J., 2020. Targeting the photoreceptor cilium for the treatment of retinal diseases. Acta Pharmacol. Sin. 41, 1410-1415.
    [72]
    Reiter, J.F.,Leroux, M.R., 2017. Genes and molecular pathways underpinning ciliopathies. Nat. Rev. Mol. Cell Biol. 18, 533-547.
    [73]
    Ross, S.E., Hemati, N., Longo, K.A., Bennett, C.N., Lucas, P.C., Erickson, R.L.,MacDougald, O.A., 2000. Inhibition of adipogenesis by wnt signaling. Science 289, 950-953.
    [74]
    Rouabhi, M., Guo, D.F., Morgan, D.A., Zhu, Z., Lopez, M., Zingman, L., Grobe, J.L.,Rahmouni, K., 2021. Bbsome ablation in sf1 neurons causes obesity without comorbidities. Mol. Metabol. 48, 101211.
    [75]
    Schou, K.B., Pedersen, L.B.,Christensen, S.T., 2015. Ins and outs of gpcr signaling in primary cilia. EMBO Rep. 16, 1099-1113.
    [76]
    Schwartz, M.W., Woods, S.C., Porte, D., Jr., Seeley, R.J.,Baskin, D.G., 2000. Central nervous system control of food intake. Nature 404, 661-671.
    [77]
    Seo, S., Baye, L.M., Schulz, N.P., Beck, J.S., Zhang, Q., Slusarski, D.C.,Sheffield, V.C., 2010. Bbs6, bbs10, and bbs12 form a complex with cct/tric family chaperonins and mediate bbsome assembly. Proc. Natl. Acad. Sci. U.S.A. 107, 1488-1493.
    [78]
    Seo, S., Guo, D.F., Bugge, K., Morgan, D.A., Rahmouni, K.,Sheffield, V.C., 2009. Requirement of bardet-biedl syndrome proteins for leptin receptor signaling. Hum. Mol. Genet. 18, 1323-1331.
    [79]
    Siljee, J.E., Wang, Y., Bernard, A.A., Ersoy, B.A., Zhang, S., Marley, A., Von Zastrow, M., Reiter, J.F.,Vaisse, C., 2018. Subcellular localization of mc4r with adcy3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity. Nat. Genet. 50, 180-185.
    [80]
    Simon, J.J., Stopyra, M.A., Monning, E., Sailer, S., Lavandier, N., Kihm, L.P., Bendszus, M., Preissl, H., Herzog, W.,Friederich, H.C., 2020. Neuroimaging of hypothalamic mechanisms related to glucose metabolism in anorexia nervosa and obesity. J. Clin. Invest. 130, 4094-4103.
    [81]
    Sims, J.S.,Lorden, J.F., 1986. Effect of paraventricular nucleus lesions on body weight, food intake and insulin levels. Behav. Brain Res. 22, 265-281.
    [82]
    Song, T., Yang, Y., Zhou, P., Ran, J., Zhang, L., Wu, X., Xie, W., Zhong, T., Liu, H., Liu, M., et al., 2022. Enkd1 promotes cp110 removal through competing with cep97 to initiate ciliogenesis. EMBO Rep. 23, e54090.
    [83]
    Spalding, K.L., Arner, E., Westermark, P.O., Bernard, S., Buchholz, B.A., Bergmann, O., Blomqvist, L., Hoffstedt, J., Naslund, E., Britton, T., et al., 2008. Dynamics of fat cell turnover in humans. Nature 453, 783-787.
    [84]
    Stratigopoulos, G., LeDuc, C.A., Cremona, M.L., Chung, W.K.,Leibel, R.L., 2011. Cut-like homeobox 1 (cux1) regulates expression of the fat mass and obesity-associated and retinitis pigmentosa gtpase regulator-interacting protein-1-like (rpgrip1l) genes and coordinates leptin receptor signaling. J. Biol. Chem. 286, 2155-2170.
    [85]
    Stratigopoulos, G., Martin Carli, J.F., O'Day, D.R., Wang, L., Leduc, C.A., Lanzano, P., Chung, W.K., Rosenbaum, M., Egli, D., Doherty, D.A., et al., 2014. Hypomorphism for rpgrip1l, a ciliary gene vicinal to the fto locus, causes increased adiposity in mice. Cell Metabol. 19, 767-779.
    [86]
    Suh, J.M., Gao, X., McKay, J., McKay, R., Salo, Z.,Graff, J.M., 2006. Hedgehog signaling plays a conserved role in inhibiting fat formation. Cell Metabol. 3, 25-34.
    [87]
    Sun, J.S., Yang, D.J., Kinyua, A.W., Yoon, S.G., Seong, J.K., Kim, J., Moon, S.J., Shin, D.M., Choi, Y.H.,Kim, K.W., 2021. Ventromedial hypothalamic primary cilia control energy and skeletal homeostasis. J. Clin. Invest. 131.
    [88]
    Tang, W., Zeve, D., Suh, J.M., Bosnakovski, D., Kyba, M., Hammer, R.E., Tallquist, M.D.,Graff, J.M., 2008. White fat progenitor cells reside in the adipose vasculature. Science 322, 583-586.
    [89]
    Tartaglia, L.A., Dembski, M., Weng, X., Deng, N., Culpepper, J., Devos, R., Richards, G.J., Campfield, L.A., Clark, F.T., Deeds, J., et al., 1995. Identification and expression cloning of a leptin receptor, ob-r. Cell 83, 1263-1271.
    [90]
    Teperino, R., Amann, S., Bayer, M., McGee, S.L., Loipetzberger, A., Connor, T., Jaeger, C., Kammerer, B., Winter, L., Wiche, G., et al., 2012. Hedgehog partial agonism drives warburg-like metabolism in muscle and brown fat. Cell 151, 414-426.
    [91]
    Vaisse, C., Reiter, J.F.,Berbari, N.F., 2017. Cilia and obesity. Cold Spring Harbor Perspect. Biol. 9.
    [92]
    Volta, F.,Gerdes, J.M., 2017. The role of primary cilia in obesity and diabetes. Ann. N. Y. Acad. Sci. 1391, 71-84.
    [93]
    Woollard, J.R., Punyashtiti, R., Richardson, S., Masyuk, T.V., Whelan, S., Huang, B.Q., Lager, D.J., vanDeursen, J., Torres, V.E., Gattone, V.H., et al., 2007. A mouse model of autosomal recessive polycystic kidney disease with biliary duct and proximal tubule dilatation. Kidney Int. 72, 328-336.
    [94]
    Wright, W.S., Longo, K.A., Dolinsky, V.W., Gerin, I., Kang, S., Bennett, C.N., Chiang, S.H., Prestwich, T.C., Gress, C., Burant, C.F., et al., 2007. Wnt10b inhibits obesity in ob/ob and agouti mice. Diabetes 56, 295-303.
    [95]
    Yamakawa, D., Katoh, D., Kasahara, K., Shiromizu, T., Matsuyama, M., Matsuda, C., Maeno, Y., Watanabe, M., Nishimura, Y., Inagaki, M., 2021. Primary cilia-dependent lipid raft/caveolin dynamics regulate adipogenesis. Cell Rep. 34, 108817.
    [96]
    Yang, D., Wu, X., Wang, W., Zhou, Y.,Wang, Z., 2022. Ciliary type iii adenylyl cyclase in the vmh is crucial for high-fat diet-induced obesity mediated by autophagy. Adv. Sci. 9, e2102568.
    [97]
    Yang, D.J., Hong, J.,Kim, K.W., 2021. Hypothalamic primary cilium: a hub for metabolic homeostasis. Exp. Mol. Med. 53, 1109-1115.
    [98]
    Yang, Y., Ran, J., Liu, M., Li, D., Li, Y., Shi, X., Meng, D., Pan, J., Ou, G., Aneja, R., et al., 2014. Cyld mediates ciliogenesis in multiple organs by deubiquitinating cep70 and inactivating hdac6. Cell Res. 24, 1342-1353.
    [99]
    Yildiz Bolukbasi, E., Mumtaz, S., Afzal, M., Woehlbier, U., Malik, S.,Tolun, A., 2018. Homozygous mutation in cep19, a gene mutated in morbid obesity, in bardet-biedl syndrome with predominant postaxial polydactyly. J. Med. Genet. 55, 189-197.
    [100]
    Yu, F., Guo, S., Li, T., Ran, J., Zhao, W., Li, D., Liu, M., Yan, X., Yang, X., Zhu, X., et al., 2019. Ciliary defects caused by dysregulation of o-glcnac modification are associated with diabetic complications. Cell Res. 29, 171-173.
    [101]
    Yu, F., Li, T., Sui, Y., Chen, Q., Yang, S., Yang, J., Hong, R., Li, D., Yan, X., Zhao, W., et al., 2020. O-glcnac transferase regulates centriole behavior and intraflagellar transport to promote ciliogenesis. Protein Cell 11, 852-857.
    [102]
    Yu, F., Ran, J.,Zhou, J., 2016. Ciliopathies: does hdac6 represent a new therapeutic target? Trends Pharmacol. Sci. 37, 114-119.
    [103]
    Zhang, M.,Assouline, J.G., 2007. Cilia containing 9 + 2 structures grown from immortalized cells. Cell Res. 17, 537-545.
    [104]
    Zhang, Q., Davenport, J.R., Croyle, M.J., Haycraft, C.J.,Yoder, B.K., 2005. Disruption of ift results in both exocrine and endocrine abnormalities in the pancreas of tg737(orpk) mutant mice. Lab. Invest. 85, 45-64.
    [105]
    Zhang, Y., Hao, J., Tarrago, M.G., Warner, G.M., Giorgadze, N., Wei, Q., Huang, Y., He, K., Chen, C., Peclat, T.R., et al., 2021. Fbf1 deficiency promotes beiging and healthy expansion of white adipose tissue. Cell Rep. 36, 109481.
    [106]
    Zheng, J., Liu, H., Zhu, L., Chen, Y., Zhao, H., Zhang, W., Li, F., Xie, L., Yan, X.,Zhu, X., 2019. Microtubule-bundling protein spef1 enables mammalian ciliary central apparatus formation. J. Mol. Cell Biol. 11, 67-77.
    [107]
    Zhu, B., Zhu, X., Wang, L., Liang, Y., Feng, Q.,Pan, J., 2017. Functional exploration of the ift-a complex in intraflagellar transport and ciliogenesis. PLoS Genet. 13, e1006627.
    [108]
    Zhu, D., Shi, S., Wang, H.,Liao, K., 2009. Growth arrest induces primary-cilium formation and sensitizes igf-1-receptor signaling during differentiation induction of 3t3-l1 preadipocytes. J. Cell Sci. 122, 2760-2768.
    [109]
    Zhu, L., Yang, X., Li, J., Jia, X., Bai, X., Zhao, Y., Cheng, W., Shu, M., Zhu, Y.,Jin, S., 2021a. Leptin gene-targeted editing in ob/ob mouse adipose tissue based on the crispr/cas9 system. J. Genet. Genomics 48, 134-146.
    [110]
    Zhu, X., Wang, J., Li, S., Lechtreck, K.,Pan, J., 2021b. Ift54 directly interacts with kinesin-ii and ift dynein to regulate anterograde intraflagellar transport. EMBO J. 40, e105781.
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