Abstract: The expression of the cell death-inducing DNA fragmentation factor α-like effector (CIDE) family including Cidea, Cideb, and Cidec was significantly increased in mouse and human models of obesity. However, there was less information on these genes’ expression in pigs. Here, we hypothesized that different fat accumulation between lean (Duroc×Landrace×Yorkshire gilts, DLY) and obese (Lantang) pigs was attributed to porcine CIDE-modulating lipid metabolism. Our data showed that Cidea and Cidec were expressed at a high level in adipose tissue, and at a relatively high level in skeletal muscle, whereas Cideb was mainly expressed in the liver in both breeds of pig. Lantang pigs had higher white adipose and skeletal muscle Cidea and Cidec mRNA abundance, and hepatic and muscle Cideb mRNA than DLY pigs. Lipid metabolism-related genes including sterol regulatory element binding protein 1c (SREBP-1c), hepatocyte nuclear factor-4α (HNF-4α), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), fatty acid synthase (FASN), diacylglycerol O-acyltransferase 1 (DGAT1), and DGAT2 showed a higher expression level in adipose tissue from obese pigs than in that from lean pigs. Lantang pigs exhibited higher mRNA abundance for liver SREBP-1c, HNF-4α, and PGC-1α, and higher skeletal muscle SREBP-1c, HNF-4α, PGC-1α, and DGAT2 expression, as compared with DLY pigs. However, the perlipin2 mRNA levels in adipose tissues, liver, and skeletal muscle were significantly lower in obese pigs than in their lean counterparts. Furthermore, plasma non-esterified fatty acid (NEFA), glucose, and triacylglycerol (TAG) levels were greater in obese pigs than in lean pigs. Finally, data from correlation analysis further found that CIDE mRNA expression was positively correlated with back fat thickness (BFT), abdominal fat mass (AFM), and the levels of NEFA, TAG, and glucose in the two breeds. Collectively, these data revealed that the porcine CIDEs possibly modulated lipid metabolism and contributed to the development of fat deposition and obesity in Lantang pigs.

肥胖型和瘦肉型猪的脂肪、肝脏及骨骼肌组织中CIDE家族基因表达水平的比较研究

[1]Abu-Elheiga, L., Oh, W., Kordari, P., et al., 2003. Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets. Proc. Natl. Acad. Sci. USA, 100(18):10207-10212.

[2]Ahima, R.S., Flier, J.S., 2000. Adipose tissue as an endocrine organ. Trends Endocrinol. Metab., 11(8):327-332.

[3]Bell, M., Wang, H., Chen, H., et al., 2008. Consequences of lipid droplet coat protein downregulation in liver cells: abnormal lipid droplet metabolism and induction of insulin resistance. Diabetes, 57(8):2037-2045.

[4]Bernlohr, D.A., Jenkins, A.E., Bennaars, A.A., 2002. Adipose tissue and lipid metabolism. In: Vance, D.E., Vance, J.E. (Eds.), Biochemistry of Lipids, Lipoproteins and Membranes, 4th Ed. Elsevier, Amsterdam, p.263-289.

[5]Chen, Z.J., Norris, J.Y., Finck, B.N., 2010. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) stimulates VLDL assembly through activation of cell death-inducing DFFA-like effector B (CideB). J. Biol. Chem., 285(34):25996-26004.

[6]Chen, Z.M., Qi, X.H., Zhang, H., et al., 2010. Changes of leptin and leptin receptor gene expression in subcutaneous fat and hypothalamus of Lantang and Landrace pigs. J. Huazhong Agric. Univ., 29(1):67-70 (in Chinese).

[7]Danesch, U., Hoeck, W., Ringold, G.M., 1992. Cloning and transcriptional regulation of a novel adipocyte-specific gene, FSP27. CAAT-enhancer-binding protein (C/EBP) and C/EBP-like proteins interact with sequences required for differentiation-dependent expression. J. Biol. Chem., 267(10):7185-7193.

[8]Girousse, A., Langin, D., 2012. Adipocyte lipases and lipid droplet-associated proteins: insight from transgenic mouse models. Int. J. Obes. (Lond.), 36(4):581-594.

[9]Gong, J., Sun, Z., Li, P., 2009. CIDE proteins and metabolic disorders. Curr. Opin. Lipidol., 20(2):121-126.

[10]Hallberg, M., Morganstein, D.L., Kiskinis, E., et al., 2008. A functional interaction between RIP140 and PGC-1α regulates the expression of the lipid droplet protein CIDEA. Mol. Cell. Biol., 28(22):6785-6795.

[11]Herzig, S., Long, F., Jhala, U.S., et al., 2001. CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature, 413(6852):179-183.

[12]Horton, J.D., Goldstein, J.L., Brown, M.S., 2002. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J. Clin. Invest., 109(9): 1125-1131.

[13]Hulver, M.W., Berggren, J.R., Cortright, R.N., et al., 2003. Skeletal muscle lipid metabolism with obesity. Am. J. Physiol. Endocrinol. Metab., 284(4):E741-E747.

[14]Inohara, N., Koseki, T., Chen, S., et al., 1998. CIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor. EMBO J., 17(9):2526-2533.

[15]Jiang, J.P., Zhou, J., Chen, J., et al., 2007. Effect of chicken egg yolk antibody against adipose tissue plasma membranes on carcass composition and lipogenic hormones and enzymes in pigs. Livestock Sci., 107(2-3):235-243.

[16]Keller, P., Petrie, J.T., de Rose, P., et al., 2008. Fat-specific protein 27 regulates storage of triacylglycerol. J. Biol. Chem., 283(21):14355-14365.

[17]Lan, L.T., Huang, L.S., Ma, J.W., et al., 2004. Experiment for comparing the performance of Erhualian pig double cross combinations and that of Duroc×(Landrace×Large Yorkshire) three-way cross combination. J. Southwest Univ. Natl., 30(6):741-744.

[18]Leonhardt, M., Langhans, W., 2004. Fatty acid oxidation and control of food intake. Physiol. Behav., 83(4):645-651.

[19]Li, J.Z., Ye, J., Xue, B., et al., 2007. Cideb regulates diet-induced obesity, liver steatosis, and insulin sensitivity by controlling lipogenesis and fatty acid oxidation. Diabetes, 56(10):2523-2532.

[20]Li, J.Z., Lei, Y., Wang, Y., et al., 2010. Control of cholesterol biosynthesis, uptake and storage in hepatocytes by Cideb. Biochim. Biophys. Acta, 1801(5):577-586.

[21]Li, X.H., Ye, J., Zhou, L.K., et al., 2012. Opposing roles of cell death-inducing DFF45-like effector B and perilipin 2 in controlling hepatic VLDL lipidation. J. Lipid Res., 53(9): 1877-1889.

[22]Li, Y.H., Lei, T., Chen, X.D., et al., 2009. Molecular cloning, chromosomal location and expression pattern of porcine CIDEa and CIDEc. Mol. Biol. Rep., 36(3):575-582.

[23]Liu, Y., Millar, J.S., Cromley, D.A., et al., 2008. Knockdown of Acyl-CoA: diacylglycerol acyltransferase 2 with antisense oligonucleotide reduces VLDL TG and ApoB secretion in mice. Biochim. Biophys. Acta, 1781(3):97-104.

[24]Lu, P., Li, D.F., Yin, J.D., et al., 2008. Flavour differences of cooked longissimus muscle from Chinese indigenous pig breeds and hybrid pig breed (Duroc×Landrace×Large White). Food Chem., 107(4):1529-1537.

[25]Malaguarnera, M., Di Rosa, M., Nicoletti, F., et al., 2009. Molecular mechanisms involved in NAFLD progression. J. Mol. Med. (Berl.), 87(7):679-695.

[26]Nishino, N., Tamori, Y., Tateya, S., et al., 2008. FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets. J. Clin. Invest., 118(8):2808-2821.

[27]Nishizuka, Y., 1992. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase. Science, 258(5082):607-614.

[28]Nordström, E.A., Rydén, M., Backlund, E.C., et al., 2005. A human-specific role of cell death-inducing DFFA (DNA fragmentation factor-α)-like effector A (CIDEA) in adipocyte lipolysis and obesity. Diabetes, 54(6):1726-1734.

[29]O'Hea, E.K., Leveille, G.A., 1969. Significance of adipose tissue and liver as sites of fatty acid synthesis in the pig and the efficiency of utilization of various substrates for lipogenesis. J. Nutr., 99(3):338-344.

[30]Shimomura, I., Bashmakov, Y., Horton, J.D., 1999. Increased levels of nuclear SREBP-1c associated with fatty livers in two mouse models of diabetes mellitus. J. Biol. Chem., 274(4):30028-30032.

[31]Singaravelu, R., Lyn, R.K., Srinivasan, P., et al., 2013. Human serum activates CIDEB-mediated lipid droplet enlargement in hepatoma cells. Biochem. Biophys. Res. Commun., 441(2):447-452.

[32]Tian, Z.M., Ma, X.Y., Yang, X.F., et al., 2016. Influence of low protein diets on gene expression of digestive enzymes and hormone secretion in the gastrointestinal tract of young weaned piglets. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 17(10):742-751.

[33]Toh, S.Y., Gong, J., Du, G., et al., 2008. Up-regulation of mitochondrial activity and acquirement of brown adipose tissue-like property in the white adipose tissue of Fsp27 deficient mice. PLoS ONE, 3(8):e2890.

[34]Vandesompele, J., de Preter, K., Pattyn, F., et al., 2002. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol., 3(7):research0034.1.

[35]Walstra, P., Merkus, G.S.M., 1995. Procedure for assessment of the lean meat percentage as a consequence of the new EU reference dissection method in pig carcass classification. Report ID-DLO 96.014, Zeist, the Netherlands.

[36]Yonezawa, T., Kurata, R., Kimura, M., et al., 2011. Which CIDE are you on? Apoptosis and energy metabolism. Mol. Biosyst., 7(1):91-100.

[37]Yu, M., Wang, H., Zhao, J., et al., 2013. Expression of CIDE proteins in clear cell renal cell carcinoma and their prognostic significance. Mol. Cell. Biochem., 378(1): 145-151.

[38]Zhou, Z., Yon Toh, S., Chen, Z., et al., 2003. Cidea-deficient mice have lean phenotype and are resistant to obesity. Nat. Genet., 35(1):49-56.