Journal of Zhejiang University-SCIENCE B

, Volume 19, Issue 11, pp 884–894 | Cite as

A high-fat diet increases body fat mass and up-regulates expression of genes related to adipogenesis and inflammation in a genetically lean pig

  • Xue-fen Yang
  • Yue-qin Qiu
  • Li Wang
  • Kai-guo Gao
  • Zong-yong JiangEmail author


Because of their physiological similarity to humans, pigs provide an excellent model for the study of obesity. This study evaluated diet-induced adiposity in genetically lean pigs and found that body weight and energy intake did not differ between controls and pigs fed the high-fat (HF) diet for three months. However, fat mass percentage, adipocyte size, concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), insulin, and leptin in plasma were significantly higher in HF pigs than in controls. The HF diet increased the expression in backfat tissue of genes responsible for cholesterol synthesis such as Insig-1 and Insig-2. Lipid metabolism-related genes including sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthase 1 (FASN1), diacylglycerol O-acyltransferase 2 (DGAT2), and fatty acid binding protein 4 (FABP4) were significantly up-regulated in backfat tissue, while the expression of proliferator-activated receptor-α (PPAR-α) and carnitine palmitoyl transferase 2 (CPT2), both involved in fatty acid oxidation, was reduced. In liver tissue, HF feeding significantly elevated the expression of SREBP-1c, FASN1, DGAT2, and hepatocyte nuclear factor-4α (HNF-4α) mRNAs. Microarray analysis further showed that the HF diet had a significant effect on the expression of 576 genes. Among these, 108 genes were related to 21 pathways, with 20 genes involved in adiposity deposition and 26 related to immune response. Our results suggest that an HF diet can induce genetically lean pigs into obesity with body fat mass expansion and adipose-related inflammation.

Key words

Genetically lean pig Diet-induced obesity High-fat diet Adiposity deposition Microarray analysis Inflammation 






发现给瘦肉型猪饲喂高脂膳食, 会引起其脂肪沉积, 同时导致肥胖及脂肪炎症。




结果表明, 高脂膳食增加瘦肉型猪的脂肪质量, 增大脂肪细胞, 而且增加血浆中总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、胰岛素和瘦素的含量。高脂膳食增加背部脂肪组织中Insig-1、Insig-2、SREBP-1c、FASN1、 DGAT2FABP4 等正调节脂肪生成的基因表达量, 但下调PPAR-αCPT2 的表达。在肝脏组织中, 高脂膳食上调SREBP-1c、FASN1、DGAT2HNF-4α 基因表达。此外, 基因芯片分析的结果发现高脂膳食上调了脂肪组织中576个基因的表达水平, 其中20个基因涉及到脂肪生成, 26 个基因与脂肪炎症相关。综上所述, 高脂膳食可以引起瘦肉型猪的脂肪沉积并导致肥胖且伴随脂肪炎症。


瘦肉型猪 膳食引起的肥胖 高脂膳食 脂肪沉积 基因芯片分析炎症 

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We gratefully acknowledge Dr. WB Currie (Cornell University, Ithaca, NY, USA) for suggestions on presentation.

Supplementary material

11585_2018_316_MOESM1_ESM.pdf (365 kb)
A high-fat diet increases body fat mass and up-regulates expression of genes related to adipogenesis and inflammation in a genetically lean pig


  1. Azorín-Ortuño M, Yáñez-Gascón MJ, González-Sarrías A, et al., 2012. Effects of long-term consumption of low doses of resveratrol on diet-induced mild hypercholesterolemia in pigs: a transcriptomic approach to disease prevention. J Nutr Biochem, 23(7):829–837. Scholar
  2. Bernlohr DA, Jenkins AE, Bennaars AA, 2002. Adipose tissue and lipid metabolism. In: Vance DE, Vance JE (Eds.), Biochemistry of Lipids, Lipoproteins and Membranes, 4th Ed. Elsevier, Amsterdam, p.263–289.Google Scholar
  3. Bortell R, Owen TA, Ignotz R, et al., 1994. TGFβ1 prevents the down-regulation of type I procollagen, fibronectin, and TGFβ1 gene expression associated with 3T3-L1 preadipocyte differentiation. J Cell Biochem, 54(2):256–263. Scholar
  4. Bray GA, Paeratakul S, Popkin BM, 2004. Dietary fat and obesity: a review of animal, clinical and epidemiological studies. Physiol Behav, 83(4):549–555. Scholar
  5. Campión J, Milagro FI, Fernández D, et al., 2006. Diferential gene expression and adiposity reduction induced by ascorbic acid supplementation in a cafeteria model of obesity. J Physiol Biochem, 62(2):71–80. Scholar
  6. Chalkley SM, Hettiarachchi M, Chisholm DJ, et al., 2002. Long-term high-fat feeding leads to severe insulin resistance but not diabetes in Wistar rats. Am J Physiol Endocrinol Metab, 282(6):e1231–E1238. Scholar
  7. Choi EH, Yang HP, Chun HS, 2012. Chitooligosaccharide ameliorates diet-induced obesity in mice and affects adipose gene expression involved in adipogenesis and inflammation. Nutr Res, 32(3):218–228. Scholar
  8. Christoffersen B, Golozoubova V, Pacini G, et al., 2013. The young Göttingen minipig as a model of childhood and adolescent obesity: influence of diet and gender. Obesity, 21(1):149–158. Scholar
  9. Gimeno RE, Klaman LD, 2005. Adipose tissue as an active endocrine organ: recent advances. Curr Opin Pharmacol, 5(2):122–128. Scholar
  10. Gregoire FM, Smas CM, Sul HS, 1998. Understanding adipocyte differentiation. Physiol Rev, 78(3):783–809. Scholar
  11. Guilford BL, Parson JC, Grote CW, et al., 2017. Increased FNDC5 is associated with insulin resistance in high fat-fed mice. Physiol Rep, 5(13):e13319. Scholar
  12. Kershaw EE, Flier JS, 2004. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab, 89(6):2548–2556.–0395CrossRefGoogle Scholar
  13. Kim Y, Park T, 2010. DNA microarrays to define and search for genes associated with obesity. Biotechnol J, 5(1): 99–112. Scholar
  14. Leitner L, Schuch K, Jürets A, et al., 2015. Immunological blockade of adipocyte inflammation caused by increased matrix metalloproteinase-cleaved osteopontin in obesity. Obesity, 23(4):779–785. Scholar
  15. Li JZ, Ye J, Xue BF, 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. Scholar
  16. Liu Y, Millar JS, Cromley DA, 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. Scholar
  17. Liu YQ, Yuan JF, Xiang L, et al., 2017. A high sucrose and high fat diet induced the development of insulin resistance in the skeletal muscle of Bama miniature pigs through the Akt/GLUT4 pathway. Exp Anim, 66(4): 387–395. Scholar
  18. Ludvigsen TP, Kirk RK, Christoffersen BØ, et al., 2015. Göttingen minipig model of diet-induced atherosclerosis: influence of mild streptozotocin-induced diabetes on lesion severity and markers of inflammation evaluated in obese, obese and diabetic, and lean control animals. J Transl Med, 13:312. Scholar
  19. Ma XY, Zheng CT, Hu YJ, et al., 2015. Dietary L-arginine supplementation affects the skeletal longissimus muscle proteome in finishing pigs. PLoS ONE, 10(1):e0117294. Scholar
  20. Malbert CH, Picq C, Divoux JL, et al., 2017. Obesityassociated alterations in glucose metabolism are reversed by chronic bilateral stimulation of the abdominal vagus nerve. Diabetes, 66:848–857. Scholar
  21. Munzberg H, 2010. Leptin-signaling pathways and leptin resistance. In: Langhans W, Geary N (Eds.), Frontiers in Eating and Weight Regulation. Karger, Switzerland, p.123–132.Google Scholar
  22. Nakajima I, Muroya S, Tanab RI, et al., 2002. Extracellular matrix development during differentiation into adipocytes with a unique increase in type V and VI collagen. Biol Cell, 94(3):197–203. Scholar
  23. O'Hea EK, Leveille GA, 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. Scholar
  24. Pasarica M, Gowronska-Kozak B, Burk D, et al., 2009. Adipose tissue collagen VI in obesity. J Clin Endocrinol Metab, 94(12):5155–5162. Scholar
  25. Qiu YQ, Yang XF, Ma XY, et al., 2017. CIDE gene expression in adipose tissue, liver, and skeletal muscle from obese and lean pigs. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 18(6):492–500. Scholar
  26. Rocha D, Plastow G, 2006. Commercial pigs: an untapped resource for human obesity research? Drug Discov Today, 11(11–12): 475–477. Scholar
  27. Rødgaard T, Stagsted J, Christoffersen BØ, et al., 2013. Orosomucoid expression profiles in liver, adipose tissues and serum of lean and obese domestic pigs, Göttingen minipigs and Ossabaw minipigs. Vet Immunol Immunopathol, 151(3–4): 325–330. Scholar
  28. Schrauwen P, Westerterp KR, 2000. The role of high-fat diets and physical activity in the regulation of body weight. Br J Nutr, 84(4):417–427. Scholar
  29. Soukas A, Cohen P, Socci ND, et al., 2000. Leptin-specific patterns of gene expression in white adipose tissue. Genes Dev, 14(8):963–980.Google Scholar
  30. Toedebusch RG, Roberts MD, Wells KD, et al., 2014. Unique transcriptomic signature of omental adipose tissue in Ossabaw swine: a model of childhood obesity. Physiol Genomics, 46(10):362–375. Scholar
  31. Weiner FR, Shah A, Smith PJ, et al., 1989. Regulation of collagen gene expression in 3T3-L1 cells. Effects of adipocyte differentiation and tumor necrosis factor α. Biochemistry, 28(9):4094–4099. Scholar
  32. Yang SC, Lin SH, Chang JS, et al., 2017. High fat diet with a high monounsaturated fatty acid and polyunsaturated/saturated fatty acid ratio suppresses body fat accumulation and weight gain in obese hamsters. Nutrients, 9(10): 1148. Scholar
  33. Yaqoob P, Sherrington EJ, Jeffery NM, et al., 1995. Comparison of the effects of a range of dietary lipids upon serum and tissue lipid composition in the rat. Int J Biochem Cell Biol, 27(3):297–310. Scholar

Copyright information

© Zhejiang University and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratory of Animal Nutrition and Feed (South China), Ministry of Agriculture / State Key Laboratory of Livestock and Poultry Breeding / Guangdong Key Laboratory of Animal Breeding and Nutrition / Guangdong Public Laboratory of Animal Breeding and Nutrition / Institute of Animal ScienceGuangdong Academy of Agricultural SciencesGuangzhouChina

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