DOI QR코드

DOI QR Code

Obesity Regulation through Gut Microbiota Modulation and Adipose Tissue Browning

장내 미생물의 조절과 지방세포의 갈색지방화를 통한 비만 조절 연구

  • Cho, Yejin (College of Medicine, Soonchunhyang University) ;
  • Shamim, Rahman Md. (Department of Microbiology, College of Medicine, Soonchunhyang University) ;
  • Kim, Yong-Sik (College of Medicine, Soonchunhyang University)
  • Received : 2019.07.11
  • Accepted : 2019.08.05
  • Published : 2019.08.30

Abstract

Obesity, represented by abnormal fat accumulation due to an imbalance between energy intake and expenditure, is a major public health issue worldwide, leading to multiple noncommunicable diseases, including atherosclerosis, hypertension, type 2 diabetes, and cancer. Diverse solutions have been proposed to combat obesity. Attention has focused on two types of adipose tissues as a promising therapeutic target in obesity: traditional brown and beige or brite. Unlike energy-storing white adipose (endocrine) tissue, traditional brown adipose tissue and beige adipose tissue have energy-dissipating thermogenic properties. Both types of tissue are present in adult humans and inducible through external stimuli, such as cold exposure, ${\beta}3$-adrenergic receptor agonists, and phytochemicals. Among these stimuli, microbiota present in the human intestinal tract participate in multiple metabolic activities. Modulation of gut microbiota may offer a potent and possibly curative strategy against various metabolic diseases. Numerous studies have focused on the effects of established antiobesity treatments on the gut microenvironment or brown-adipose-tissue activation. In this review, we focus mainly on stimuli known to alleviate obesity, weight gain, and metabolic diseases, in addition to known and possible inter-relations between gut microbiota modulation and similar interventions and adipose tissue browning. The findings may pave the way toward new strategies against obesity.

비만은 에너지 섭취와 소비의 불균형으로 인해 유발되는 비정상적인 지방 축적으로, 근래에 다양한 만성질환을 초래하는 주요 국제 보건 문제로 부상하였다. 이러한 이유로, 비만 문제에 대한 여러 해결책들이 제시되고 있다. 에너지를 저장하며 내분비 작용을 하는 백색 지방과 달리 열을 생성하여 에너지를 발산하는 두 종류의 지방조직인 갈색 지방과 베이지색 지방이 성인에 존재하며 외부 자극에 의해 유도될 수 있다는 것이 밝혀진 이래로, 이들은 비만 치료의 유망한 표적으로서 각광받고 있다. 이러한 외부 자극 중, 인간 장관계에서 인간과 공존하는 장내 미생물총은 다양한 대사 작용에 참여하며, 이를 조절하는 것이 여러 대사 질환의 치료에 유력한 작용을 할 것으로 보인다. 따라서, 다양한 연구에서 항비만 치료가 장내 미생물 환경 전환이나 갈색 지방 조직 활성화에 미치는 영향에 초점을 맞추고 있다. 본 총설에서는 비만과 체중 증가, 대사 질환을 해소하는 것으로 알려진 자극과, 장내 미생물총의 변화나 갈색지방의 활성화를 야기하는 자극과, 이 자극들과 장내 미생물총의 조작, 지방조직의 갈색화 사이에서 알려져 있거나 있을 수 있는 상관관계를 중점적으로 다루고자 한다.

Keywords

References

  1. Agerholm-Larsen, L., Raben, A., Haulrik, N., Hansen, A. S., Manders, M. and Astrup, A. 2000. Effect of 8 week intake of probiotic milk products on risk factors for cardiovascular diseases. Eur. J. Clin. Nutr. 54, 288-297. https://doi.org/10.1038/sj.ejcn.1600937
  2. Alberdi, G., Rodriguez, V. M., Miranda, J., Macarulla, M. T., Churruca, I. and Portillo, M. P. 2013. Thermogenesis is involved in the body-fat lowering effects of resveratrol in rats. Food Chem. 141, 1530-1535. https://doi.org/10.1016/j.foodchem.2013.03.085
  3. Alisi, A., Bedogni, G., Baviera, G., Giorgio, V., Porro, E., Paris, C., Giammaria, P., Reali, L., Anania, F. and Nobili, V. 2014. Randomised clinical trial: The beneficial effects of vsl#3 in obese children with non-alcoholic steatohepatitis. Aliment. Pharmacol. Ther. 39, 1276-1285. https://doi.org/10.1111/apt.12758
  4. Allen, J. M., Mailing, L. J., Niemiro, G. M., Moore, R., Cook, M. D., White, B. A., Holscher, H. D. and Woods, J. A. 2018. Exercise alters gut microbiota composition and function in lean and obese humans. Med. Sci. Sports Exerc. 50, 747-757.
  5. Aller, R., De Luis, D., Izaola, O., Conde, R., Gonzalez Sagrado, M., Primo, D., De La Fuente, B. and Gonzalez, J. 2011. Effect of a probiotic on liver aminotransferases in nonalcoholic fatty liver disease patients: A double blind randomized clinical trial. Eur. Rev. Med. Pharmacol. Sci. 15, 1090-1095.
  6. An, H. M., Park, S. Y., Lee, D. K., Kim, J. R., Cha, M. K., Lee, S. W., Lim, H. T., Kim, K. J. and Ha, N. J. 2011. Antiobesity and lipid-lowering effects of bifidobacterium spp. In high fat diet-induced obese rats. Lipids Health Dis. 10, 116. https://doi.org/10.1186/1476-511X-10-116
  7. An, Y., Li, Y., Wang, X., Chen, Z., Xu, H., Wu, L., Li, S., Wang, C., Luan, W., Wang, X., Liu, M., Tang, X. and Yu, L. 2018. Cordycepin reduces weight through regulating gut microbiota in high-fat diet-induced obese rats. Lipids Health Dis. 17, 276. https://doi.org/10.1186/s12944-018-0910-6
  8. Anhe, F. F., Nachbar, R. T., Varin, T. V., Trottier, J., Dudonne, S., Le Barz, M., Feutry, P., Pilon, G., Barbier, O. and Desjardins, Y. 2019. Treatment with camu camu (myrciaria dubia) prevents obesity by altering the gut microbiota and increasing energy expenditure in diet-induced obese mice. Gut 68, 453-464. https://doi.org/10.1136/gutjnl-2017-315565
  9. Apovian, C. M., Aronne, L. J., Bessesen, D. H., McDonnell, M. E., Murad, M. H., Pagotto, U., Ryan, D. H., Still, C. D. and Endocrine, S. 2015. Pharmacological management of obesity: An endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 100, 342-362. https://doi.org/10.1210/jc.2014-3415
  10. Arias, N., Pico, C., Teresa Macarulla, M., Oliver, P., Miranda, J., Palou, A. and Portillo, M. P. 2017. A combination of resveratrol and quercetin induces browning in white adipose tissue of rats fed an obesogenic diet. Obesity 25, 111-121. https://doi.org/10.1002/oby.21706
  11. Askari, H., Rajani, S. F., Poorebrahim, M., Haghi-Aminjan, H., Raeis-Abdollahi, E. and Abdollahi, M. 2018. A glance at the therapeutic potential of irisin against diseases involving inflammation, oxidative stress, and apoptosis: An introductory review. Pharmacol. Res. 129, 44-55. https://doi.org/10.1016/j.phrs.2018.01.012
  12. Azhar, Y., Parmar, A., Miller, C. N., Samuels, J. S. and Rayalam, S. 2016. Phytochemicals as novel agents for the induction of browning in white adipose tissue. Nutr. Metab. (Lond.) 13, 89. https://doi.org/10.1186/s12986-016-0150-6
  13. Bahler, L., Verberne, H. J., Admiraal, W. M., Stok, W. J., Soeters, M. R., Hoekstra, J. B. and Holleman, F. 2016. Differences in sympathetic nervous stimulation of brown adipose tissue between the young and old, and the lean and obese. J. Nucl. Med. 57, 372-377. https://doi.org/10.2967/jnumed.115.165829
  14. Bomhof, M. R., Saha, D. C., Reid, D. T., Paul, H. A. and Reimer, R. A. 2014. Combined effects of oligofructose and bifidobacterium animalis on gut microbiota and glycemia in obese rats. Obesity 22, 763-771. https://doi.org/10.1002/oby.20632
  15. Brahe, L. K., Le Chatelier, E., Prifti, E., Pons, N., Kennedy, S., Blædel, T., Hakansson, J., Dalsgaard, T. K., Hansen, T. and Pedersen, O. 2015. Dietary modulation of the gut microbiota-a randomised controlled trial in obese postmenopausal women. Br. J. Nutr. 114, 406-417. https://doi.org/10.1017/S0007114515001786
  16. Brooks, A. W., Priya, S., Blekhman, R. and Bordenstein, S. R. 2018. Gut microbiota diversity across ethnicities in the united states. PLoS Biol. 16, e2006842. https://doi.org/10.1371/journal.pbio.2006842
  17. Cani, P. D., Joly, E., Horsmans, Y. and Delzenne, N. M. 2006. Oligofructose promotes satiety in healthy human: A pilot study. Eur. J. Clin. Nutr. 60, 567-572. https://doi.org/10.1038/sj.ejcn.1602350
  18. Cani, P. D., Lecourt, E., Dewulf, E. M., Sohet, F. M., Pachikian, B. D., Naslain, D., De Backer, F., Neyrinck, A. M. and Delzenne, N. M. 2009. Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal. Am. J. Clin. Nutr. 90, 1236-1243. https://doi.org/10.3945/ajcn.2009.28095
  19. Cao, L., Choi, E. Y., Liu, X., Martin, A., Wang, C., Xu, X. and During, M. J. 2011. White to brown fat phenotypic switch induced by genetic and environmental activation of a hypothalamic-adipocyte axis. Cell Metab. 14, 324-338. https://doi.org/10.1016/j.cmet.2011.06.020
  20. Cerdo, T., Garcia-Santos, J. A., M, G. B. and Campoy, C. 2019. The role of probiotics and prebiotics in the prevention and treatment of obesity. Nutrients 11, 635. https://doi.org/10.3390/nu11030635
  21. Chen, L. H., Chen, Y. H., Cheng, K. C., Chien, T. Y., Chan, C. H., Tsao, S. P. and Huang, H. Y. 2018. Antiobesity effect of lactobacillus reuteri 263 associated with energy metabolism remodeling of white adipose tissue in high-energy- diet-fed rats. J. Nutr. Biochem. 54, 87-94. https://doi.org/10.1016/j.jnutbio.2017.11.004
  22. Choque Delgado, G. T. and Tamashiro, W. 2018. Role of prebiotics in regulation of microbiota and prevention of obesity. Food Res. Int. 113, 183-188. https://doi.org/10.1016/j.foodres.2018.07.013
  23. Chung, H. J., Jae, G. Y., Lee, I. A., Liu, M. J., Shen, Y. F., Sharma, S. P., Jamal, M. A., Yoo, J. H., Kim, H. J. and Hong, S. T. 2016. Intestinal removal of free fatty acids from hosts by lactobacilli for the treatment of obesity. FEBS Open Bio. 6, 64-76. https://doi.org/10.1002/2211-5463.12024
  24. Clarke, G., Stilling, R. M., Kennedy, P. J., Stanton, C., Cryan, J. F. and Dinan, T. G. 2014. Minireview: Gut microbiota: The neglected endocrine organ. Mol. Endocrinol. 28, 1221-1238. https://doi.org/10.1210/me.2014-1108
  25. Cummings, J. H. 1981. Short chain fatty acids in the human colon. Gut 22, 763-779. https://doi.org/10.1136/gut.22.9.763
  26. Cypess, A. M., Weiner, L. S., Roberts-Toler, C., Franquet Elia, E., Kessler, S. H., Kahn, P. A., English, J., Chatman, K., Trauger, S. A., Doria, A. and Kolodny, G. M. 2015. Activation of human brown adipose tissue by a beta3-adrenergic receptor agonist. Cell Metab. 21, 33-38. https://doi.org/10.1016/j.cmet.2014.12.009
  27. Dardmeh, F., Alipour, H., Gazerani, P., van der Horst, G., Brandsborg, E. and Nielsen, H. I. 2017. Lactobacillus rhamnosus pb01 (dsm 14870) supplementation affects markers of sperm kinematic parameters in a diet-induced obesity mice model. PloS One 12, e0185964. https://doi.org/10.1371/journal.pone.0185964
  28. de Carvalho Marchesin, J., Celiberto, L. S., Orlando, A. B., de Medeiros, A. I., Pinto, R. A., Zuanon, J. A. S., Spolidorio, L. C., dos Santos, A., Taranto, M. P. and Cavallini, D. C. U. 2018. A soy-based probiotic drink modulates the microbiota and reduces body weight gain in diet-induced obese mice. J. Funct. Foods 48, 302-313. https://doi.org/10.1016/j.jff.2018.07.010
  29. De Lorenzo, A., Costacurta, M., Merra, G., Gualtieri, P., Cioccoloni, G., Marchetti, M., Varvaras, D., Docimo, R. and Di Renzo, L. 2017. Can psychobiotics intake modulate psychological profile and body composition of women affected by normal weight obese syndrome and obesity? A double blind randomized clinical trial. J. Transl. Med. 15, 135. https://doi.org/10.1186/s12967-017-1236-2
  30. Dehghan, P., Gargari, B. P., Jafar-Abadi, M. A. and Aliasgharzadeh, A. 2014. Inulin controls inflammation and metabolic endotoxemia in women with type 2 diabetes mellitus: A randomized-controlled clinical trial. Int. J. Food Sci. Nutr. 65, 117-123. https://doi.org/10.3109/09637486.2013.836738
  31. den Besten, G., van Eunen, K., Groen, A. K., Venema, K., Reijngoud, D. J. and Bakker, B. M. 2013. The role of shortchain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J. Lipid Res. 54, 2325-2340. https://doi.org/10.1194/jlr.R036012
  32. Dewal, R. S. and Stanford, K. I. 2019. Effects of exercise on brown and beige adipocytes. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1864, 71-78. https://doi.org/10.1016/j.bbalip.2018.04.013
  33. Djuric, Z. 2017. Obesity-associated cancer risk: The role of intestinal microbiota in the etiology of the host proinflammatory state. Transl. Res. 179, 155-167. https://doi.org/10.1016/j.trsl.2016.07.017
  34. Edrisi, F., Salehi, M., Ahmadi, A., Fararoei, M., Rusta, F. and Mahmoodianfard, S. 2018. Effects of supplementation with rice husk powder and rice bran on inflammatory factors in overweight and obese adults following an energy-restricted diet: A randomized controlled trial. Eur. J. Nutr. 57, 833-843. https://doi.org/10.1007/s00394-017-1555-3
  35. Everard, A., Lazarevic, V., Derrien, M., Girard, M., Muccioli, G. G., Neyrinck, A. M., Possemiers, S., Van Holle, A., Francois, P. and de Vos, W. M. 2011. Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes 60, 2775-2786. https://doi.org/10.2337/db11-0227
  36. Fabbiano, S., Suarez-Zamorano, N., Chevalier, C., Lazarevic, V., Kieser, S., Rigo, D., Leo, S., Veyrat-Durebex, C., Gaia, N., Maresca, M., Merkler, D., Gomez de Aguero, M., Macpherson, A., Schrenzel, J. and Trajkovski, M. 2018. Functional gut microbiota remodeling contributes to the caloric restriction-induced metabolic improvements. Cell Metab. 28, 907-921.e907. https://doi.org/10.1016/j.cmet.2018.08.005
  37. Fabbiano, S., Suarez-Zamorano, N., Rigo, D., Veyrat-Durebex, C., Stevanovic Dokic, A., Colin, D. J. and Trajkovski, M. 2016. Caloric restriction leads to browning of white adipose tissue through type 2 immune signaling. Cell Metab. 24, 434-446. https://doi.org/10.1016/j.cmet.2016.07.023
  38. Fak, F. and Backhed, F. 2012. Lactobacillus reuteri prevents diet-induced obesity, but not atherosclerosis, in a strain dependent fashion in apoe-/- mice. PLoS One 7, e46837. https://doi.org/10.1371/journal.pone.0046837
  39. Famouri, F., Shariat, Z., Hashemipour, M., Keikha, M. and Kelishadi, R. 2017. Effects of probiotics on nonalcoholic fatty liver disease in obese children and adolescents. J. Pediatr. Gastroenterol. Nutr. 64, 413-417. https://doi.org/10.1097/MPG.0000000000001422
  40. Fathi, Y., Faghih, S., Zibaeenezhad, M. J. and Tabatabaei, S. H. 2016. Kefir drink leads to a similar weight loss, compared with milk, in a dairy-rich non-energy-restricted diet in overweight or obese premenopausal women: A randomized controlled trial. Eur. J. Nutr. 55, 295-304. https://doi.org/10.1007/s00394-015-0846-9
  41. Fontane, L., Benaiges, D., Goday, A., Llaurado, G. and Pedro-Botet, J. 2018. Influence of the microbiota and probiotics in obesity. Clin. Investig. Arterioscler. 30, 271-279.
  42. Genta, S., Cabrera, W., Habib, N., Pons, J., Carillo, I. M., Grau, A. and Sanchez, S. 2009. Yacon syrup: Beneficial effects on obesity and insulin resistance in humans. Clin. Nutr. 28, 182-187. https://doi.org/10.1016/j.clnu.2009.01.013
  43. Gobel, R. J., Larsen, N., Jakobsen, M., Molgaard, C. and Michaelsen, K. F. 2012. Probiotics to adolescents with obesity: Effects on inflammation and metabolic syndrome. J. Pediatr. Gastroenterol. Nutr. 55, 673-678. https://doi.org/10.1097/MPG.0b013e318263066c
  44. Gomes, A. C., de Sousa, R. G. M., Botelho, P. B., Gomes, T. L. N., Prada, P. O. and Mota, J. F. 2017. The additional effects of a probiotic mix on abdominal adiposity and antioxidant status: A double-blind, randomized trial. Obesity 25, 30-38. https://doi.org/10.1002/oby.21671
  45. Halkjaer, S. I., Nilas, L., Carlsen, E. M., Cortes, D., Halldorsson, T. I., Olsen, S. F., Pedersen, A. E., Krogfelt, K. A. and Petersen, A. M. 2016. Effects of probiotics (vivomixx(R)) in obese pregnant women and their newborn: Study protocol for a randomized controlled trial. Trials 17, 491. https://doi.org/10.1186/s13063-016-1617-5
  46. He, X., Zheng, N., He, J., Liu, C., Feng, J., Jia, W. and Li, H. 2017. Gut microbiota modulation attenuated the hypolipidemic effect of simvastatin in high-fat/cholesterol-diet fed mice. J. Proteome Res. 16, 1900-1910. https://doi.org/10.1021/acs.jproteome.6b00984
  47. Heaton, J. M. 1972. The distribution of brown adipose tissue in the human. J. Anat. 112, 35-39.
  48. Higashikawa, F., Noda, M., Awaya, T., Danshiitsoodol, N., Matoba, Y., Kumagai, T. and Sugiyama, M. 2016. Antiobesity effect of pediococcus pentosaceus lp28 on overweight subjects: A randomized, double-blind, placebo-controlled clinical trial. Eur. J. Clin. Nutr. 70, 582-587. https://doi.org/10.1038/ejcn.2016.17
  49. Hill, J. O., Wyatt, H. R. and Peters, J. C. 2012. Energy balance and obesity. Circulation 126, 126-132. https://doi.org/10.1161/CIRCULATIONAHA.111.087213
  50. Hume, M. P., Nicolucci, A. C. and Reimer, R. A. 2017. Prebiotic supplementation improves appetite control in children with overweight and obesity: A randomized controlled trial. Am. J. Clin. Nutr. 105, 790-799. https://doi.org/10.3945/ajcn.116.140947
  51. Ikeda, K., Maretich, P. and Kajimura, S. 2018. The common and distinct features of brown and beige adipocytes. Trends Endocrinol. Metab. 29, 191-200. https://doi.org/10.1016/j.tem.2018.01.001
  52. Jung, S. P., Lee, K. M., Kang, J. H., Yun, S. I., Park, H. O., Moon, Y. and Kim, J. Y. 2013. Effect of lactobacillus gasseri bnr17 on overweight and obese adults: A randomized, double-blind clinical trial. Kor. J. Fam. Med. 34, 80. https://doi.org/10.4082/kjfm.2013.34.2.80
  53. Jung, S., Lee, Y. J., Kim, M., Kim, M., Kwak, J. H., Lee, J. W., Ahn, Y. T., Sim, J. H. and Lee, J. H. 2015. Supplementation with two probiotic strains, lactobacillus curvatus hy7601 and lactobacillus plantarum ky1032, reduced body adiposity and lp-pla2 activity in overweight subjects. J. Funct. Foods 19, 744-752. https://doi.org/10.1016/j.jff.2015.10.006
  54. Kaddurah-Daouk, R., Baillie, R. A., Zhu, H., Zeng, Z. B., Wiest, M. M., Nguyen, U. T., Wojnoonski, K., Watkins, S. M., Trupp, M. and Krauss, R. M. 2011. Enteric microbiome metabolites correlate with response to simvastatin treatment. PLoS One 6, e25482. https://doi.org/10.1371/journal.pone.0025482
  55. Kadooka, Y., Sato, M., Imaizumi, K., Ogawa, A., Ikuyama, K., Akai, Y., Okano, M., Kagoshima, M. and Tsuchida, T. 2010. Regulation of abdominal adiposity by probiotics (lactobacillus gasseri sbt2055) in adults with obese tendencies in a randomized controlled trial. Eur. J. Clin. Nutr. 64, 636-643. https://doi.org/10.1038/ejcn.2010.19
  56. Kahan, S. 2016. Overweight and obesity management strategies. Am. J. Manag. Care 22, s186-196.
  57. Karbaschian, Z., Mokhtari, Z., Pazouki, A., Kabir, A., Hedayati, M., Moghadam, S. S., Mirmiran, P. and Hekmatdoost, A. 2018. Probiotic supplementation in morbid obese patients undergoing one anastomosis gastric bypass-mini gastric bypass (oagb-mgb) surgery: A randomized, double-blind, placebo-controlled, clinical trial. Obes. Surg. 28, 2874-2885. https://doi.org/10.1007/s11695-018-3280-2
  58. Kershaw, E. E. and Flier, J. S. 2004. Adipose tissue as an endocrine organ. J. Clin. Endocrinol. Metab. 89, 2548-2556. https://doi.org/10.1210/jc.2004-0395
  59. Kim, J., Yun, J. M., Kim, M. K., Kwon, O. and Cho, B. 2018. Lactobacillus gasseri bnr17 supplementation reduces the visceral fat accumulation and waist circumference in obese adults: A randomized, double-blind, placebo-controlled trial. J. Med. Food 21, 454-461. https://doi.org/10.1089/jmf.2017.3937
  60. Kim, M., Kim, M., Kang, M., Yoo, H. J., Kim, M. S., Ahn, Y. T., Sim, J. H., Jee, S. H. and Lee, J. H. 2017. Effects of weight loss using supplementation with lactobacillus strains on body fat and medium-chain acylcarnitines in overweight individuals. Food Funct. 8, 250-261. https://doi.org/10.1039/C6FO00993J
  61. Kondo, S., Xiao, J. Z., Satoh, T., Odamaki, T., Takahashi, S., Sugahara, H., Yaeshima, T., Iwatsuki, K., Kamei, A. and Abe, K. 2010. Antiobesity effects of bifidobacterium breve strain b-3 supplementation in a mouse model with high-fat diet-induced obesity. Biosci. Biotechnol. Biochem. 74, 1656-1661. https://doi.org/10.1271/bbb.100267
  62. Kong, C., Gao, R., Yan, X., Huang, L. and Qin, H. 2018. Probiotics improve gut microbiota dysbiosis in obese mice fed a high-fat or high-sucrose diet. Nutrition 60, 175-184
  63. Larsen, N., Vogensen, F. K., Gobel, R. J., Michaelsen, K. F., Forssten, S. D., Lahtinen, S. J. and Jakobsen, M. 2013. Effect of lactobacillus salivarius ls-33 on fecal microbiota in obese adolescents. Clin. Nutr. 32, 935-940. https://doi.org/10.1016/j.clnu.2013.02.007
  64. Leber, B., Tripolt, N. J., Blattl, D., Eder, M., Wascher, T. C., Pieber, T. R., Stauber, R., Sourij, H., Oettl, K. and Stadlbauer, V. 2012. The influence of probiotic supplementation on gut permeability in patients with metabolic syndrome: An open label, randomized pilot study. Eur. J. Clin. Nutr. 66, 1110-1115. https://doi.org/10.1038/ejcn.2012.103
  65. Li, S., Li, J., Mao, G., Wu, T., Lin, D., Hu, Y., Ye, X., Tian, D., Chai, W., Linhardt, R. J. and Chen, S. 2019. Fucosylated chondroitin sulfate from isostichopus badionotus alleviates metabolic syndromes and gut microbiota dysbiosis induced by high-fat and high-fructose diet. Int. J. Biol. Macromol. 124, 377-388. https://doi.org/10.1016/j.ijbiomac.2018.11.167
  66. Li, X., Song, Y., Ma, X., Zhang, Y., Liu, X., Cheng, L., Han, D., Shi, Y., Sun, Q. and Yang, C. 2018. Lactobacillus plantarum and lactobacillus fermentum alone or in combination regulate intestinal flora composition and systemic immunity to alleviate obesity syndrome in high-fat diet rat. Int. J. Food Sci. Technol. 53, 137-146. https://doi.org/10.1111/ijfs.13567
  67. Liao, A. H., Jiang, C. B., Li, C. C., Chuang, H. C., Chiang Chiau, J. S., Chan, W. T., Yeung, C. Y., Cheng, M. L. and Lee, H. C. 2017. Combining ultrasound and lactobacilli treatment for high-fat-diet-induced obesity in mice. J. Anim. Physiol. Anim. Nutr. 101, 703-712. https://doi.org/10.1111/jpn.12499
  68. Lindsay, K. L., Kennelly, M., Culliton, M., Smith, T., Maguire, O. C., Shanahan, F., Brennan, L. and McAuliffe, F. M. 2014. Probiotics in obese pregnancy do not reduce maternal fasting glucose: A double-blind, placebo-controlled, randomized trial (probiotics in pregnancy study). Am. J. Clin. Nutr. 99, 1432-1439. https://doi.org/10.3945/ajcn.113.079723
  69. Lu, H. Y., Zeng, H., Zhang, L., Porres, J. M. and Cheng, W. H. 2018. Fecal fermentation products of common bean-derived fiber inhibit c/ebpalpha and ppargamma expression and lipid accumulation but stimulate ppardelta and ucp2 expression in the adipogenesis of 3t3-l1 cells. J. Nutr. Biochem. 60, 9-15. https://doi.org/10.1016/j.jnutbio.2018.06.004
  70. Lucas, C., Barnich, N. and Nguyen, H. T. T. 2017. Microbiota, inflammation and colorectal cancer. Int. J. Mol. Sci. 18, 1310. https://doi.org/10.3390/ijms18061310
  71. Luoto, R., Kalliomaki, M., Laitinen, K. and Isolauri, E. 2010. The impact of perinatal probiotic intervention on the development of overweight and obesity: Follow-up study from birth to 10 years. Int. J. Obes. (Lond.) 34, 1531-1537. https://doi.org/10.1038/ijo.2010.50
  72. Macfarlane, G. T. and Macfarlane, S. 2012. Bacteria, colonic fermentation, and gastrointestinal health. J. AOAC Int. 95, 50-60. https://doi.org/10.5740/jaoacint.SGE_Macfarlane
  73. Madjd, A., Taylor, M. A., Mousavi, N., Delavari, A., Malekzadeh, R., Macdonald, I. A. and Farshchi, H. R. 2015. Comparison of the effect of daily consumption of probiotic compared with low-fat conventional yogurt on weight loss in healthy obese women following an energy-restricted diet: A randomized controlled trial. Am. J. Clin. Nutr. 103, 323-329. https://doi.org/10.3945/ajcn.115.120170
  74. Mahadzir, M. D. A., Shyam, S., Barua, A., Krishnappa, P. and Ramamurthy, S. 2017. Effect of probiotic microbial cell preparation (mcp) on fasting blood glucose, body weight, waist circumference, and faecal short chain fatty acids among overweight malaysian adults: A pilot randomised controlled trial of 4 weeks. Malays. J. Nutr. 23, 329-341.
  75. Minami, J., Kondo, S., Yanagisawa, N., Odamaki, T., Xiao, J. Z., Abe, F., Nakajima, S., Hamamoto, Y., Saitoh, S. and Shimoda, T. 2015. Oral administration of bifidobacterium breve b-3 modifies metabolic functions in adults with obese tendencies in a randomised controlled trial. J. Nutr. Sci. 4, e17. https://doi.org/10.1017/jns.2015.5
  76. Minami, J., Iwabuchi, N., Tanaka, M., Yamauchi, K., Xiao, J. Z., Abe, F. and Sakane, N. 2018. Effects of bifidobacterium breve b-3 on body fat reductions in pre-obese adults: A randomized, double-blind, placebo-controlled trial. Biosci. Microbiota Food Health 37, 67-75. https://doi.org/10.12938/bmfh.18-001
  77. Mischke, M., Arora, T., Tims, S., Engels, E., Sommer, N., van Limpt, K., Baars, A., Oozeer, R., Oosting, A. and Backhed, F. 2018. Specific synbiotics in early life protect against dietinduced obesity in adult mice. Diabetes Obes. Metab. 20, 1408-1418. https://doi.org/10.1111/dom.13240
  78. Miyoshi, M., Ogawa, A., Higurashi, S. and Kadooka, Y. 2014. Anti-obesity effect of lactobacillus gasseri sbt2055 accompanied by inhibition of pro-inflammatory gene expression in the visceral adipose tissue in diet-induced obese mice. Eur. J. Nutr. 53, 599-606. https://doi.org/10.1007/s00394-013-0568-9
  79. Mohammadi-Sartang, M., Bellissimo, N., de Zepetnek, J. T., Brett, N., Mazloomi, S., Fararouie, M., Bedeltavana, A., Famouri, M. and Mazloom, Z. 2018. The effect of daily fortified yogurt consumption on weight loss in adults with metabolic syndrome: A 10-week randomized controlled trial. Nutr. Metab. Cardiovasc. Dis. 28, 565-574. https://doi.org/10.1016/j.numecd.2018.03.001
  80. Mosqueda-Solis, A., Sanchez, J., Portillo, M. P., Palou, A. and Pico, C. 2018. Combination of capsaicin and hesperidin reduces the effectiveness of each compound to decrease the adipocyte size and to induce browning features in adipose tissue of western diet fed rats. J. Agric. Food Chem. 66, 9679-9689. https://doi.org/10.1021/acs.jafc.8b02611
  81. Murakami, Y., Ojima-Kato, T., Saburi, W., Mori, H., Matsui, H., Tanabe, S. and Suzuki, T. 2015. Supplemental epilactose prevents metabolic disorders through uncoupling protein-1 induction in the skeletal muscle of mice fed high-fat diets. Br. J. Nutr. 114, 1774-1783. https://doi.org/10.1017/S0007114515003505
  82. Mykhal'chyshyn, H., Bodnar, P. and Kobyliak, N. 2013. Effect of probiotics on proinflammatory cytokines level in patients with type 2 diabetes and nonalcoholic fatty liver disease. Lik. Sprava. 2, 56-62.
  83. Nedergaard, J. and Cannon, B. 2014. The browning of white adipose tissue: Some burning issues. Cell Metab. 20, 396-407. https://doi.org/10.1016/j.cmet.2014.07.005
  84. Neyrinck, A. M., Bindels, L. B., Geurts, L., Van Hul, M., Cani, P. D. and Delzenne, N. M. 2017. A polyphenolic extract from green tea leaves activates fat browning in high-fat-diet-induced obese mice. J. Nutr. Biochem. 49, 15-21. https://doi.org/10.1016/j.jnutbio.2017.07.008
  85. Nicolucci, A. C., Hume, M. P., Martinez, I., Mayengbam, S., Walter, J. and Reimer, R. A. 2017. Prebiotics reduce body fat and alter intestinal microbiota in children who are overweight or with obesity. Gastroenterology 153, 711-722. https://doi.org/10.1053/j.gastro.2017.05.055
  86. Nihei, N., Okamoto, H., Furune, T., Ikuta, N., Sasaki, K., Rimbach, G., Yoshikawa, Y. and Terao, K. 2018. Dietary ${\alpha}$-cyclodextrin modifies gut microbiota and reduces fat accumulation in high-fat-diet-fed obese mice. BioFactors 44, 336-347. https://doi.org/10.1002/biof.1429
  87. Ohyama, K., Nogusa, Y., Shinoda, K., Suzuki, K., Bannai, M. and Kajimura, S. 2016. A synergistic antiobesity effect by a combination of capsinoids and cold temperature through promoting beige adipocyte biogenesis. Diabetes 65, 1410-1423. https://doi.org/10.2337/db15-0662
  88. Omar, J. M., Chan, Y. M., Jones, M. L., Prakash, S. and Jones, P. J. H. 2013. Lactobacillus fermentum and lactobacillus amylovorus as probiotics alter body adiposity and gut microflora in healthy persons. J. Funct. Foods 5, 116-123. https://doi.org/10.1016/j.jff.2012.09.001
  89. World Health Organization. Noncommunicable diseases country profiles 2018: World Health Organization, 2018.
  90. World Health Organization. 2018. Obesity and overweight. Retrieved from https://www.who.int/news-room/factsheets/detail/obesity-and-overweight.
  91. Osterberg, K. L., Boutagy, N. E., McMillan, R. P., Stevens, J. R., Frisard, M. I., Kavanaugh, J. W., Davy, B. M., Davy, K. P. and Hulver, M. W. 2015. Probiotic supplementation attenuates increases in body mass and fat mass during high-fat diet in healthy young adults. Obesity 23, 2364-2370. https://doi.org/10.1002/oby.21230
  92. Panteliou, E. and Miras, A. D. 2017. What is the role of bariatric surgery in the management of obesity? Climacteric 20, 97-102. https://doi.org/10.1080/13697137.2017.1262638
  93. Park, D. Y., Ahn, Y. T., Park, S. H., Huh, C. S., Yoo, S. R., Yu, R., Sung, M. K., McGregor, R. A. and Choi, M. S. 2013. Supplementation of lactobacillus curvatus hy7601 and lactobacillus plantarum ky1032 in diet-induced obese mice is associated with gut microbial changes and reduction in obesity. PLoS One 8, e59470. https://doi.org/10.1371/journal.pone.0059470
  94. Park, J. E., Oh, S. H. and Cha, Y. S. 2014. Lactobacillus plantarum lg42 isolated from gajami sik-hae decreases body and fat pad weights in diet-induced obese mice. J. Appl. Microbiol. 116, 145-156. https://doi.org/10.1111/jam.12354
  95. Parnell, J. A. and Reimer, R. A. 2010. Effect of prebiotic fibre supplementation on hepatic gene expression and serum lipids: A dose-response study in jcr: La-cp rats. Br. J. Nutr. 103, 1577-1584. https://doi.org/10.1017/S0007114509993539
  96. Parnell, J. A. and Reimer, R. A. 2009. Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide yy in overweight and obese adults. Am. J. Clin. Nutr. 89, 1751-1759. https://doi.org/10.3945/ajcn.2009.27465
  97. Pedret, A., Valls, R. M., Calderon-Perez, L., Llaurado, E., Companys, J., Pla-Paga, L., Moragas, A., Martin-Lujan, F., Ortega, Y. and Giralt, M. 2018. Effects of daily consumption of the probiotic bifidobacterium animalis subsp. Lactis cect 8145 on anthropometric adiposity biomarkers in abdominally obese subjects: A randomized controlled trial. Int. J. Obes. doi: 10.1038/s41366-018-0220-0.
  98. Pyra, K. A., Saha, D. C. and Reimer, R. A. 2012. Prebiotic fiber increases hepatic acetyl coa carboxylase phosphorylation and suppresses glucose-dependent insulinotropic polypeptide secretion more effectively when used with metformin in obese rats. J. Nutr. 142, 213-220. https://doi.org/10.3945/jn.111.147132
  99. Rajkumar, H., Mahmood, N., Kumar, M., Varikuti, S. R., Challa, H. R. and Myakala, S. P. 2014. Effect of probiotic (vsl# 3) and omega-3 on lipid profile, insulin sensitivity, inflammatory markers, and gut colonization in overweight adults: A randomized, controlled trial. Mediators Inflamm. 2014, 348959.
  100. Reimer, R. A., Willis, H. J., Tunnicliffe, J. M., Park, H., Madsen, K. L. and Soto-Vaca, A. 2017. Inulin-type fructans and whey protein both modulate appetite but only fructans alter gut microbiota in adults with overweight/obesity: A randomized controlled trial. Mol. Nutr. Food Res. 61, 1700484. https://doi.org/10.1002/mnfr.201700484
  101. Respondek, F., Gerard, P., Bossis, M., Boschat, L., Bruneau, A., Rabot, S., Wagner, A. and Martin, J. C. 2013. Short-chain fructo-oligosaccharides modulate intestinal microbiota and metabolic parameters of humanized gnotobiotic diet induced obesity mice. PLoS One 8, e71026. https://doi.org/10.1371/journal.pone.0071026
  102. Reynes, B., Palou, M., Rodriguez, A. M. and Palou, A. 2018. Regulation of adaptive thermogenesis and browning by prebiotics and postbiotics. Front. Physiol. 9, 1908. https://doi.org/10.3389/fphys.2018.01908
  103. Russo, F., Linsalata, M., Clemente, C., Chiloiro, M., Orlando, A., Marconi, E., Chimienti, G. and Riezzo, G. 2012. Inulinenriched pasta improves intestinal permeability and modifies the circulating levels of zonulin and glucagon-like peptide 2 in healthy young volunteers. Nutr. Res. 32, 940-946. https://doi.org/10.1016/j.nutres.2012.09.010
  104. Saez-Lara, M. J., Robles-Sanchez, C., Ruiz-Ojeda, F. J., Plaza-Diaz, J. and Gil, A. 2016. Effects of probiotics and synbiotics on obesity, insulin resistance syndrome, type 2 diabetes and non-alcoholic fatty liver disease: A review of human clinical trials. Int. J. Mol. Sci. 17, 928. https://doi.org/10.3390/ijms17060928
  105. Sanchez, M., Darimont, C., Panahi, S., Drapeau, V., Marette, A., Taylor, V., Dore, J. and Tremblay, A. 2017. Effects of a diet-based weight-reducing program with probiotic supplementation on satiety efficiency, eating behaviour traits, and psychosocial behaviours in obese individuals. Nutrients 9, 284. https://doi.org/10.3390/nu9030284
  106. Sanchis-Chorda, J., del Pulgar, E. M. G., Carrasco-Luna, J., Benitez-Paez, A., Sanz, Y. and Codoner-Franch, P. 2018. Bifidobacterium pseudocatenulatum cect 7765 supplementation improves inflammatory status in insulin-resistant obese children. Eur. J. Nutr. 1-12.
  107. Serrano, A., Asnani-Kishnani, M., Rodriguez, A. M., Palou, A., Ribot, J. and Bonet, M. L. 2018. Programming of the beige phenotype in white adipose tissue of adult mice by mild resveratrol and nicotinamide riboside supplementations in early postnatal life. Mol. Nutr. Food Res. 62, 1800463. https://doi.org/10.1002/mnfr.201800463
  108. Sharafedtinov, K. K., Plotnikova, O. A., Alexeeva, R. I., Sentsova, T. B., Songisepp, E., Stsepetova, J., Smidt, I. and Mikelsaar, M. 2013. Hypocaloric diet supplemented with probiotic cheese improves body mass index and blood pressure indices of obese hypertensive patients-a randomized double-blind placebo-controlled pilot study. Nutrition 12, 138. https://doi.org/10.1186/1475-2891-12-138
  109. Shin, J. H., Nam, M. H., Lee, H., Lee, J. S., Kim, H., Chung, M. J. and Seo, J. G. 2018. Amelioration of obesity-related characteristics by a probiotic formulation in a high-fat diet-induced obese rat model. Eur. J. Nutr. 57, 2081-2090. https://doi.org/10.1007/s00394-017-1481-4
  110. Silvester, A. J., Aseer, K. R. and Yun, J. W. 2019. Dietary polyphenols and their roles in fat browning. J. Nutr. Biochem. 64, 1-12. https://doi.org/10.1016/j.jnutbio.2018.09.028
  111. Sivamaruthi, B. S., Kesika, P., Suganthy, N. and Chaiyasut, C. 2019. A review on role of microbiome in obesity and antiobesity properties of probiotic supplements. Biomed Res. Int. 2019, 3291367.
  112. Skulachev, V. P. 1998. Uncoupling: New approaches to an old problem of bioenergetics. Biochim. Biophys. Acta Bioenerg. 1363, 100-124. https://doi.org/10.1016/S0005-2728(97)00091-1
  113. Staley, C., Weingarden, A. R., Khoruts, A. and Sadowsky, M. J. 2017. Interaction of gut microbiota with bile acid metabolism and its influence on disease states. Appl. Microbiol. Biotechnol. 101, 47-64. https://doi.org/10.1007/s00253-016-8006-6
  114. Stenman, L. K., Lehtinen, M. J., Meland, N., Christensen, J. E., Yeung, N., Saarinen, M. T., Courtney, M., Burcelin, R., Lahdeaho, M. L. and Linros, J. 2016. Probiotic with or without fiber controls body fat mass, associated with serum zonulin, in overweight and obese adults-randomized controlled trial. EBioMedicine 13, 190-200. https://doi.org/10.1016/j.ebiom.2016.10.036
  115. Stojanovic, O., Kieser, S. and Trajkovski, M. 2018. Common traits between the beige fat-inducing stimuli. Curr. Opin. Cell Biol. 55, 67-73. https://doi.org/10.1016/j.ceb.2018.05.011
  116. Szulinska, M., Łoniewski, I., van Hemert, S., Sobieska, M. and Bogdanski, P. 2018. Dose-dependent effects of multispecies probiotic supplementation on the lipopolysaccharide (lps) level and cardiometabolic profile in obese postmenopausal women: A 12-week randomized clinical trial. Nutrients 10, 773. https://doi.org/10.3390/nu10060773
  117. Thyagarajan, B. and Foster, M. T. 2017. Beiging of white adipose tissue as a therapeutic strategy for weight loss in humans. Horm. Mol. Biol. Clin. Investig. 31, doi: 10.1515/hmbci-2017-0016.
  118. Tseng, Y. H., Kokkotou, E., Schulz, T. J., Huang, T. L., Winnay, J. N., Taniguchi, C. M., Tran, T. T., Suzuki, R., Espinoza, D. O., Yamamoto, Y., Ahrens, M. J., Dudley, A. T., Norris, A. W., Kulkarni, R. N. and Kahn, C. R. 2008. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454, 1000-1004. https://doi.org/10.1038/nature07221
  119. Vajro, P., Mandato, C., Licenziati, M. R., Franzese, A., Vitale, D. F., Lenta, S., Caropreso, M., Vallone, G. and Meli, R. 2011. Effects of lactobacillus rhamnosus strain gg in pediatric obesity-related liver disease. J. Pediatr. Gastroenterol. Nutr. 52, 740-743. https://doi.org/10.1097/MPG.0b013e31821f9b85
  120. van Marken Lichtenbelt, W. D., Vanhommerig, J. W., Smulders, N. M., Drossaerts, J. M., Kemerink, G. J., Bouvy, N. D., Schrauwen, P. and Teule, G. J. 2009. Cold-activated brown adipose tissue in healthy men. N. Engl. J. Med. 360, 1500-1508. https://doi.org/10.1056/NEJMoa0808718
  121. Verbrugghe, A., Hesta, M., Gommeren, K., Daminet, S., Wuyts, B., Buyse, J. and Janssens, G. P. 2009. Oligofructose and inulin modulate glucose and amino acid metabolism through propionate production in normal-weight and obese cats. Br. J. Nutr. 102, 694-702. https://doi.org/10.1017/S0007114509288982
  122. Verhoef, S. P., Meyer, D. and Westerterp, K. R. 2011. Effects of oligofructose on appetite profile, glucagon-like peptide 1 and peptide yy3-36 concentrations and energy intake. Br. J. Nutr. 106, 1757-1762. https://doi.org/10.1017/S0007114511002194
  123. Virtanen, K. A., Lidell, M. E., Orava, J., Heglind, M., Westergren, R., Niemi, T., Taittonen, M., Laine, J., Savisto, N. J., Enerback, S. and Nuutila, P. 2009. Functional brown adipose tissue in healthy adults. N. Engl. J. Med. 360, 1518-1525. https://doi.org/10.1056/NEJMoa0808949
  124. Wang, E. A., Israel, D. I., Kelly, S. and Luxenberg, D. P. 1993. Bone morphogenetic protein-2 causes commitment and differentiation in c3h10t1/2 and 3t3 cells. Growth Factors 9, 57-71. https://doi.org/10.3109/08977199308991582
  125. Wang, Z. B., Xin, S. S., Ding, L. N., Ding, W. Y., Hou, Y. L., Liu, C. Q. and Zhang, X. D. 2019. The potential role of probiotics in controlling overweight/obesity and associated metabolic parameters in adults: A systematic review and meta-analysis. Evid. Based Complement. Alternat. Med. 2019, 3862971.
  126. Weiner, J., Hankir, M., Heiker, J. T., Fenske, W. and Krause, K. 2017. Thyroid hormones and browning of adipose tissue. Mol. Cell. Endocrinol. 458, 156-159. https://doi.org/10.1016/j.mce.2017.01.011
  127. Weitkunat, K., Stuhlmann, C., Postel, A., Rumberger, S., Fankhanel, M., Woting, A., Petzke, K. J., Gohlke, S., Schulz, T. J. and Blaut, M. 2017. Short-chain fatty acids and inulin, but not guar gum, prevent diet-induced obesity and insulin resistance through differential mechanisms in mice. Sci. Rep. 7, 6109. https://doi.org/10.1038/s41598-017-06447-x
  128. Whelan, K., Efthymiou, L., Judd, P. A., Preedy, V. R. and Taylor, M. A. 2006. Appetite during consumption of enteral formula as a sole source of nutrition: The effect of supplementing pea-fibre and fructo-oligosaccharides. Br. J. Nutr. 96, 350-356. https://doi.org/10.1079/BJN20061791
  129. Woodard, G. A., Encarnacion, B., Downey, J. R., Peraza, J., Chong, K., Hernandez-Boussard, T. and Morton, J. M. 2009. Probiotics improve outcomes after roux-en-y gastric bypass surgery: A prospective randomized trial. J. Gastrointest. Surg. 13, 1198-1204. https://doi.org/10.1007/s11605-009-0891-x
  130. Xue, B., Rim, J. S., Hogan, J. C., Coulter, A. A., Koza, R. A. and Kozak, L. P. 2007. Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat. J. Lipid Res. 48, 41-51. https://doi.org/10.1194/jlr.M600287-JLR200
  131. Yin, Y. N., Yu, Q. F., Fu, N., Liu, X. W. and Lu, F. G. 2010. Effects of four bifidobacteria on obesity in high-fat diet induced rats. World J. Gastroenterol. 16, 3394-3401. https://doi.org/10.3748/wjg.v16.i27.3394
  132. You, Y., Han, X., Guo, J., Guo, Y., Yin, M., Liu, G., Huang, W. and Zhan, J. 2018. Cyanidin-3-glucoside attenuates high-fat and high-fructose diet-induced obesity by promoting the thermogenic capacity of brown adipose tissue. J. Funct. Foods 41, 62-71. https://doi.org/10.1016/j.jff.2017.12.025
  133. You, Y., Yuan, X., Liu, X., Liang, C., Meng, M., Huang, Y., Han, X., Guo, J., Guo, Y. and Ren, C. 2017. Cyanidin-3-glucoside increases whole body energy metabolism by upregulating brown adipose tissue mitochondrial function. Mol. Nutr. Food Res. 61, 1700261. https://doi.org/10.1002/mnfr.201700261
  134. Zarrati, M., Salehi, E., Nourijelyani, K., Mofid, V., Zadeh, M. J., Najafi, F., Ghaflati, Z., Bidad, K., Chamari, M., Karimi, M. and Shidfar, F. 2014. Effects of probiotic yogurt on fat distribution and gene expression of proinflammatory factors in peripheral blood mononuclear cells in overweight and obese people with or without weight-loss diet. J. Am. Coll. Nutr. 33, 417-425. https://doi.org/10.1080/07315724.2013.874937
  135. Zhuang, P., Shou, Q., Lu, Y., Wang, G., Qiu, J., Wang, J., He, L., Chen, J., Jiao, J. and Zhang, Y. 2017. Arachidonic acid sex-dependently affects obesity through linking gut microbiota-driven inflammation to hypothalamus-adiposeliver axis. Biochim. Biophys. Acta Mol. Basis Dis. 1863, 2715-2726. https://doi.org/10.1016/j.bbadis.2017.07.003
  136. Zietak, M., Kovatcheva-Datchary, P., Markiewicz, L. H., Stahlman, M., Kozak, L. P. and Backhed, F. 2016. Altered microbiota contributes to reduced diet-induced obesity upon cold exposure. Cell Metab. 23, 1216-1223. https://doi.org/10.1016/j.cmet.2016.05.001
  137. Zietak, M. and Kozak, L. P. 2016. Bile acids induce uncoupling protein 1-dependent thermogenesis and stimulate energy expenditure at thermoneutrality in mice. Am. J. Physiol. Endocrinol. Metab. 310, E346-354. https://doi.org/10.1152/ajpendo.00485.2015