Skip to main content Accessibility help
×
Home

Acute and chronic cold exposure differentially affects the browning of porcine white adipose tissue

  • Y. Gao (a1), N. R. Qimuge (a1), J. Qin (a1), R. Cai (a1), X. Li (a1), G. Y. Chu (a1), W. J. Pang (a1) and G. S. Yang (a1)...

Abstract

Piglets are characteristically cold intolerant and thus susceptible to high mortality. However, browning of white adipose tissue (WAT) can induce non-shivering thermogenesis as a potential strategy to facilitate the animal’s response to cold. Whether cold exposure can induce browning of subcutaneous WAT (sWAT) in piglets in a similar manner as it can in humans remains largely unknown. In this study, piglets were exposed to acute cold (4°C, 10 h) or chronic cold exposure (8°C, 15 days), and the genes and proteins of uncoupling protein 1 (UCP1)-dependent and independent thermogenesis, mitochondrial biogenesis, lipogenic and lipolytic processes were analysed. Interestingly, acute cold exposure induced browning of porcine sWAT, smaller adipocytes and the upregulated expression of UCP1, PGC1α, PGC1β, C/EBPβ, Cidea, UCP3, CKMT1 and PM20D1. Conversely, chronic cold exposure impaired the browning process, reduced mitochondrial numbers and the expression of browning markers, including UCP1, PGC1α and PRDM16. The present study demonstrated that acute cold exposure (but not chronic cold exposure) induces porcine sWAT browning. Thus, browning of porcine sWAT could be a novel strategy to balance the body temperature of piglets, and thus could be protective against cold exposure.

Copyright

Corresponding author

References

Hide All
Balsbaugh, RK, Curtis, SE, Meyer, RC and Norton, HW 1986. Cold resistance and environmental temperature preference in diarrheic piglets. Journal of Animal Science 62, 315326.
Bellinger, DA, Merricks, EP and Nichols, TC 2006. Swine models of type 2 diabetes mellitus: insulin resistance, glucose tolerance, and cardiovascular complications. Institute for Laboratory Animal Research Journal 47, 243258.
Bi, P, Shan, T, Liu, W, Yue, F, Yang, X, Liang, XR, Wang, J, Li, J, Carlesso, N, Liu, X and Kuang, S 2014. Inhibition of notch signaling promotes browning of white adipose tissue and ameliorates obesity. Nature Medicine 20, 911918.
Collins, S 2011. Β-Adrenoceptor signaling networks in adipocytes for recruiting stored fat and energy expenditure. Frontiers in Endocrinology (Lausanne) 2, 102.
Cypess, AM, Weiner, LS, Roberts-Toler, C, Franquet, EE, Kessler, SH, Kahn, PA, English, J, Chatman, K, Trauger, SA, Doria, A and Kolodny, GM 2015. Activation of human brown adipose tissue by a beta3-adrenergic receptor agonist. Cell Metabolism 21, 3338.
Dodd, GT, Decherf, S, Loh, K, Simonds, SE, Wiede, F, Balland, E, Merry, TL, Munzberg, H, Zhang, ZY, Kahn, BB, Neel, BG, Bence, KK, Andrews, ZB, Cowley, MA and Tiganis, T 2015. Leptin and insulin act on POMC neurons to promote the browning of white fat. Cell 160, 88104.
Fedorenko, A, Lishko, PV and Kirichok, Y 2012. Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria. Cell 151, 400413.
Harms, M and Seale, P 2013. Brown and beige fat: development, function and therapeutic potential. Nature Medicine 19, 12521263.
Jespersen, NZ, Larsen, TJ, Peijs, L, Daugaard, S, Homoe, P, Loft, A, de Jong, J, Mathur, N, Cannon, B, Nedergaard, J, Pedersen, BK, Moller, K and Scheele, C 2013. A classical brown adipose tissue mRNA signature partly overlaps with brite in the supraclavicular region of adult humans. Cell Metabolism 17, 798805.
Kajimura, S, Spiegelman, BM and Seale, P 2015. Brown and beige fat: physiological roles beyond heat generation. Cell Metabolism 22, 546559.
Kazak, L, Chouchani, ET, Jedrychowski, MP, Erickson, BK, Shinoda, K, Cohen, P, Vetrivelan, R, Lu, GZ, Laznik-Bogoslavski, D, Hasenfuss, SC, Kajimura, S, Gygi, SP and Spiegelman, BM 2015. A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat. Cell 163, 643655.
Lin, J, Cao, C, Tao, C, Ye, R, Dong, M, Zheng, Q, Wang, C, Jiang, X, Qin, G, Yan, C, Li, K, Speakman, JR, Wang, Y, Jin, W and Zhao, J 2017. Cold adaptation in pigs depends on UCP3 in beige adipocytes. Journal ofMolecular Cell Biology 2017, 112.
Long, JZ, Svensson, KJ, Bateman, LA, Lin, H, Kamenecka, T, Lokurkar, IA, Lou, J, Rao, RR, Chang, MR, Jedrychowski, MP, Paulo, JA, Gygi, SP, Griffin, PR, Nomura, DK and Spiegelman, BM 2016. The secreted enzyme PM20D1 regulates lipidated amino acid uncouplers of mitochondria. Cell 166, 424435.
Lowell, BB and Spiegelman, BM 2000. Towards a molecular understanding of adaptive thermogenesis. Nature 404, 652660.
Puigserver, P and Spiegelman, BM 2003. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocrine Reviews 24, 7890.
Rosenwald, M, Perdikari, A, Rulicke, T and Wolfrum, C 2013. Bi-directional interconversion of brite and white adipocytes. Nature Cell Biology 15, 659667.
Seale, P and Lazar, MA 2009. Brown fat in humans: turning up the heat on obesity. Diabetes 58, 14821484.
Seki, T, Hosaka, K, Lim, S, Fischer, C, Honek, J, Yang, Y, Andersson, P, Nakamura, M, Naslund, E, Yla-Herttuala, S, Sun, M, Iwamoto, H, Li, X, Liu, Y, Samani, NJ and Cao, Y 2016. Endothelial PDGF-CC regulates angiogenesis-dependent thermogenesis in beige fat. Nature Communications 7, 12152.
Shabalina, IG, Petrovic, N, de Jong, JM, Kalinovich, AV, Cannon, B and Nedergaard, J 2013. UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic. Cell Reports 5, 11961203.
Sidossis, LS, Porter, C, Saraf, MK, Borsheim, E, Radhakrishnan, RS, Chao, T, Ali, A, Chondronikola, M, Mlcak, R, Finnerty, CC, Hawkins, HK, Toliver-Kinsky, T and Herndon, DN 2015. Browning of subcutaneous white adipose tissue in humans after severe adrenergic stress. Cell Metabolism 22, 219227.
Spurlock, ME and Gabler, NK 2008. The development of porcine models of obesity and the metabolic syndrome. The Journal of Nutrition 138, 397402.
van der Lans, AA, Hoeks, J, Brans, B, Vijgen, GH, Visser, MG, Vosselman, MJ, Hansen, J, Jorgensen, JA, Wu, J, Mottaghy, FM, Schrauwen, P and van Marken, LW 2013. Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. Journal of Clinical Investigation 123, 33953403.
Wang, WS and Seale, P 2016. Control of brown and beige fat development. Nature Reviews Molecular Cell Biology 17, 691702.
Wu, J, Bostrom, P, Sparks, LM, Ye, L, Choi, JH, Giang, AH, Khandekar, M, Virtanen, KA, Nuutila, P, Schaart, G, Huang, K, Tu, H, van Marken, LW, Hoeks, J, Enerback, S, Schrauwen, P and Spiegelman, BM 2012. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150, 366376.
Wu, ZD, Puigserver, P, Andersson, U, Zhang, CY, Adelmant, G, Mootha, V, Troy, A, Cinti, S, Lowell, B, Scarpulla, RC and Spiegelman, BM 1999. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98, 115124.
Xue, Y, Petrovic, N, Cao, R, Larsson, O, Lim, S, Chen, S, Feldmann, HM, Liang, Z, Zhu, Z, Nedergaard, J, Cannon, B and Cao, Y 2009. Hypoxia-independent angiogenesis in adipose tissues during cold acclimation. Cell Metabolism 9, 99109.
Xue, Y, Xu, X, Zhang, XQ, Farokhzad, OC and Langer, R 2016. Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles. Proceedings of the National Academy of Sciences of the United States of America 113, 5552–5557.
Yoneshiro, T, Aita, S, Matsushita, M, Kayahara, T, Kameya, T, Kawai, Y, Iwanaga, T and Saito, M 2013. Recruited brown adipose tissue as an antiobesity agent in humans. Journal of Clinical Investigation 123, 34043408.
Yoneshiro, T, Aita, S, Matsushita, M, Okamatsu-Ogura, Y, Kameya, T, Kawai, Y, Miyagawa, M, Tsujisaki, M and Saito, M 2011. Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans. Obesity 19, 17551760.

Keywords

Type Description Title
WORD
Supplementary materials

Gao et al supplementary material
Figures S1-S6

 Word (106.6 MB)
106.6 MB

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed