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Adipocyte and cell biology

Regulation of thermogenic capacity in brown and white adipocytes by the prebiotic high-esterified pectin and its postbiotic acetate



High-esterified pectin (HEP) is a prebiotic able to modulate gut microbiota, associated with health-promoting metabolic effects in glucose and lipid metabolism and adipostatic hormone sensitivity. Possible effects regulating adaptive thermogenesis and energy waste are poorly known. Therefore, we aimed to study how physiological supplementation with HEP is able to affect microbiota, energy metabolism and adaptive thermogenic capacity, and to contribute to the healthier phenotype promoted by HEP supplementation, as previously shown. We also attempted to decipher some of the mechanisms involved in the HEP effects, including in vitro experiments.

Subjects and experimental design

We used a model of metabolic malprogramming consisting of the progeny of rats with mild calorie restriction during pregnancy, both under control diet and an obesogenic (high-sucrose) diet, supplemented with HEP, combined with in vitro experiments in primary cultured brown and white adipocytes treated with the postbiotic acetate.


Our main findings suggest that chronic HEP supplementation induces markers of brown and white adipose tissue thermogenic capacity, accompanied by a decrease in energy efficiency, and prevention of weight gain under an obesogenic diet. We also show that HEP promotes an increase in beneficial bacteria in the gut and peripheral levels of acetate. Moreover, in vitro acetate can improve adipokine production, and increase thermogenic capacity and browning in brown and white adipocytes, respectively, which could be part of the protection mechanism against excess weight gain observed in vivo.


HEP and acetate stand out as prebiotic/postbiotic active compounds able to modulate both brown-adipocyte metabolism and browning and protect against obesity.

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  1. 1.

    Hartstra AV, Bouter KE, Bäckhed F, Nieuwdorp M. Insights into the role of the microbiome in obesity and type 2 diabetes. Diabetes Care. 2015;38:159–65.

    CAS  PubMed  Google Scholar 

  2. 2.

    Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14:491–502.

    PubMed  PubMed Central  Google Scholar 

  3. 3.

    Adam CL, Williams PA, Garden KE, Thomson LM, Ross AW. Dose-dependent effects of a soluble dietary fibre (pectin) on food intake, adiposity, gut hypertrophy and gut satiety hormone secretion in rats. PLoS ONE. 2015;10:e0115438.

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Hamaker BR, Tuncil YE. A perspective on the complexity of dietary fiber structures and their potential effect on the gut microbiota. J Mol Biol. 2014;426:3838–50.

    CAS  PubMed  Google Scholar 

  5. 5.

    Palou M, Sánchez J, García-Carrizo F, Palou A, Picó C. Pectin supplementation in rats mitigates age-related impairment in insulin and leptin sensitivity independently of reducing food intake. Mol Nutr Food Res. 2015;59:2022–33.

    CAS  PubMed  Google Scholar 

  6. 6.

    Sanchez D, Muguerza B, Moulay L, Hernandez R, Miguel M, Aleixandre A. Highly methoxylated pectin improves insulin resistance and other cardiometabolic risk factors in Zucker fatty rats. J Agric Food Chem. 2008;56:3574–81.

    CAS  PubMed  Google Scholar 

  7. 7.

    Canfora EE, Jocken JW, Blaak EE. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat Rev Endocrinol. 2015;11:577–91.

    CAS  PubMed  Google Scholar 

  8. 8.

    Oh YS, Jun HS. Role of bioactive food components in diabetes prevention: effects on Beta-cell function and preservation. Nutr Metab Insights. 2014;7:51–9.

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Galanakis CM. Nutraceutical and functional food components: effects of innovative processing techniques. London, UK: Academic Press; 2017. p. 1.

    Google Scholar 

  10. 10.

    Garcia-Carrizo F, Pico C, Rodriguez AM, Palou A. High-esterified pectin reverses metabolic malprogramming, improving sensitivity to adipostatic/adipokine hormones. J Agric Food Chem. 2019;67:3633–42.

    CAS  PubMed  Google Scholar 

  11. 11.

    Palou M, Priego T, Sánchez J, Palou A, Picó C. Sexual dimorphism in the lasting effects of moderate caloric restriction during gestation on energy homeostasis in rats is related with fetal programming of insulin and leptin resistance. Nutr Metab. 2010;7:69.

    Google Scholar 

  12. 12.

    Palou M, Konieczna J, Torrens JM, Sánchez J, Priego T, Fernandes ML, et al. Impaired insulin and leptin sensitivity in the offspring of moderate caloric-restricted dams during gestation is early programmed. J Nutr Biochem. 2012;23:1627–39.

    CAS  PubMed  Google Scholar 

  13. 13.

    Nedergaard J, Cannon B. The browning of white adipose tissue: some burning issues. Cell Metab. 2014;20:396–407.

    CAS  PubMed  Google Scholar 

  14. 14.

    Palou A, Pico C, Bonet ML, Oliver P. The uncoupling protein, thermogenin. Int J Biochem Cell Biol. 1998;30:7–11.

    CAS  PubMed  Google Scholar 

  15. 15.

    Rodriguez AM, Palou A. Uncoupling proteins: gender-dependence and their relation to body weight control. Int J Obes Relat Metab Disord. 2004;28:327–9.

    CAS  PubMed  Google Scholar 

  16. 16.

    Dongowski G, Lorenz A, Proll J. The degree of methylation influences the degradation of pectin in the intestinal tract of rats and in vitro. J Nutr. 2002;132:1935–44.

    CAS  PubMed  Google Scholar 

  17. 17.

    Fåk F, Jakobsdottir G, Kulcinskaja E, Marungruang N, Matziouridou C, Nilsson U, et al. The physico-chemical properties of dietary fibre determine metabolic responses, short-chain fatty acid profiles and gut microbiota composition in rats fed low- and high-fat diets. PloS ONE. 2015;10:e0127252.

    PubMed  PubMed Central  Google Scholar 

  18. 18.

    Chaplin A, Parra P, Serra F, Palou A. Conjugated linoleic acid supplementation under a high-fat diet modulates stomach protein expression and intestinal microbiota in adult mice. PloS ONE. 2015;10:e0125091.

    PubMed  PubMed Central  Google Scholar 

  19. 19.

    An HM, Park SY, Lee DKoK, Kim JR, Cha MK, Lee SW, et al. Antiobesity and lipid-lowering effects of Bifidobacterium spp. in high fat diet-induced obese rats. Lipids Health Dis. 2011;10:116.

    PubMed  PubMed Central  Google Scholar 

  20. 20.

    Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci USA. 2013;110:9066–71.

    CAS  Google Scholar 

  21. 21.

    Fukuda S, Toh H, Hase K, Oshima K, Nakanishi Y, Yoshimura K, et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature. 2011;469:543–7.

    CAS  PubMed  Google Scholar 

  22. 22.

    Lecomte V, Kaakoush NO, Maloney CA, Raipuria M, Huinao KD, Mitchell HM, et al. Changes in gut microbiota in rats fed a high fat diet correlate with obesity-associated metabolic parameters. PloS ONE. 2015;10:e0126931.

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Neyrinck AM, Possemiers S, Druart C, Van de Wiele T, De Backer F, Cani PD, et al. Prebiotic effects of wheat arabinoxylan related to the increase in bifidobacteria, Roseburia and Bacteroides/Prevotella in diet-induced obese mice. PloS ONE. 2011;6:e20944.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Koleva PT, Bridgman SL, Kozyrskyj AL. The infant gut microbiome: evidence for obesity risk and dietary intervention. Nutrients. 2015;7:2237–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Parnell JA, Reimer RA. Prebiotic fiber modulation of the gut microbiota improves risk factors for obesity and the metabolic syndrome. Gut Microbes. 2012;3:29–34.

    PubMed  PubMed Central  Google Scholar 

  26. 26.

    Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, et al. Host-gut microbiota metabolic interactions. Science. 2012;336:1262–7.

    CAS  PubMed  Google Scholar 

  27. 27.

    Jakobsdottir G, Nyman M, Fåk F. Designing future prebiotic fiber to target the metabolic syndrome. Nutrition. 2014;30:497–502.

    CAS  PubMed  Google Scholar 

  28. 28.

    Jakobsdottir G, Jädert C, Holm L, Nyman ME. Propionic and butyric acids, formed in the caecum of rats fed highly fermentable dietary fibre, are reflected in portal and aortic serum. Br J Nutr. 2013;110:1565–72.

    CAS  PubMed  Google Scholar 

  29. 29.

    Palou M, Priego T, Romero M, Szostaczuk N, Konieczna J, Cabrer C, et al. Moderate calorie restriction during gestation programs offspring for lower BAT thermogenic capacity driven by thyroid and sympathetic signaling. Int J Obes. 2015;39:339–45.

    CAS  Google Scholar 

  30. 30.

    García AP, Palou M, Sánchez J, Priego T, Palou A, Picó C. Moderate caloric restriction during gestation in rats alters adipose tissue sympathetic innervation and later adiposity in offspring. PloS ONE. 2011;6:e17313.

    PubMed  PubMed Central  Google Scholar 

  31. 31.

    Giordano A, Frontini A, Murano I, Tonello C, Marino MA, Carruba MO, et al. Regional-dependent increase of sympathetic innervation in rat white adipose tissue during prolonged fasting. J Histochem Cytochem. 2005;53:679–87.

    CAS  PubMed  Google Scholar 

  32. 32.

    Townsend KL, Tseng Y-HH. Brown fat fuel utilization and thermogenesis. Trends Endocrinol Metab. 2014;25:168–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L, Daniels D, et al. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem. 2003;278:11312–9.

    CAS  PubMed  Google Scholar 

  34. 34.

    Kalinovich AV, de Jong JM, Cannon B, Nedergaard J. UCP1 in adipose tissues: two steps to full browning. Biochimie. 2017;134:127–37.

    CAS  PubMed  Google Scholar 

  35. 35.

    Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481:463–8.

    PubMed  PubMed Central  Google Scholar 

  36. 36.

    Petrovic N, Shabalina IG, Timmons JA, Cannon B, Nedergaard J. Thermogenically competent nonadrenergic recruitment in brown preadipocytes by a PPARgamma agonist. Am J Physiol Endocrinol Metab. 2008;295:96.

    Google Scholar 

  37. 37.

    Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T, et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat Commun. 2013;4:1829.

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Ortega-Molina A, Efeyan A, Lopez-Guadamillas E, Muñoz-Martin M, Gómez-López G, Cañamero M, et al. Pten positively regulates brown adipose function, energy expenditure, and longevity. Cell Metab. 2012;15:382–94.

    CAS  PubMed  Google Scholar 

  39. 39.

    Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84:277–59.

    CAS  PubMed  Google Scholar 

  40. 40.

    Urs S, Harrington A, Liaw L, Small D. Selective expression of an aP2/fatty acid binding protein 4-Cre transgene in non-adipogenic tissues during embryonic development. Transgenic Res. 2006;15:647–53.

    CAS  PubMed  Google Scholar 

  41. 41.

    Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B, Nedergaard J. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem. 2010;285:7153–64.

    CAS  PubMed  Google Scholar 

  42. 42.

    Aberdein N, Schweizer M, Ball D. Sodium acetate decreases phosphorylation of hormone sensitive lipase in isoproterenol-stimulated 3T3-L1 mature adipocytes. Adipocyte. 2014;3:121–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Adam CL, Williams PA, Dalby MJ, Garden K, Thomson LM, Richardson AJ, et al. Different types of soluble fermentable dietary fibre decrease food intake, body weight gain and adiposity in young adult male rats. Nutr Metab. 2014;11:36.

    Google Scholar 

  44. 44.

    Slavin J. Fiber and prebiotics: mechanisms and health benefits. Nutrients. 2013;5:1417–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Bonet ML, Oliver P, Palou A. Pharmacological and nutritional agents promoting browning of white adipose tissue. Biochim et Biophys acta. 2013;1831:969–85.

    CAS  Google Scholar 

  46. 46.

    Chevalier C, Stojanovic O, Colin DJ, Suarez-Zamorano N, Tarallo V, Veyrat-Durebex C, et al. Gut microbiota orchestrates energy homeostasis during cold. Cell. 2015;163:1360–74.

    CAS  PubMed  Google Scholar 

  47. 47.

    Li G, Xie C, Lu S, Nichols RG, Tian Y, Li L, et al. Intermittent fasting promotes white adipose browning and decreases obesity by shaping the gut microbiota. Cell Metab. 2017;26:672–85.e4.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Reynes B, Palou M, Rodriguez AM, Palou A. Regulation of adaptive thermogenesis and browning by prebiotics and postbiotics. Front Physiol. 2018;9:1908.

    PubMed  Google Scholar 

  49. 49.

    Zietak M, Kozak LP. Bile acids induce uncoupling protein 1-dependent thermogenesis and stimulate energy expenditure at thermoneutrality in mice. Am J Physiol Endocrinol Metab. 2016;310:E346–54.

    PubMed  Google Scholar 

  50. 50.

    Albrecht E, Norheim F, Thiede B, Holen T, Ohashi T, Schering L, et al. Irisin - a myth rather than an exercise-inducible myokine. Sci Rep. 2015;5:8889.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Wu J, Boström P, Sparks LM, Ye L, Choi JH, Giang A-HH, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 2012;150:366–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Rosenwald M, Perdikari A, Rülicke T, Wolfrum C. Bi-directional interconversion of brite and white adipocytes. Nat Cell Biol. 2013;15:659–67.

    CAS  PubMed  Google Scholar 

  53. 53.

    Ge H, Li X, Weiszmann J, Wang P, Baribault H, Chen J-LL, et al. Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids. Endocrinology. 2008;149:4519–26.

    CAS  PubMed  Google Scholar 

  54. 54.

    Hong Y-HH, Nishimura Y, Hishikawa D, Tsuzuki H, Miyahara H, Gotoh C, et al. Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology. 2005;146:5092–9.

    CAS  PubMed  Google Scholar 

  55. 55.

    Perry RJ, Peng L, Barry NA, Cline GW, Zhang D, Cardone RL, et al. Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome. Nature. 2016;534:213–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Trent CM, Blaser MJ. Microbially produced acetate: a "missing link" in understanding obesity? Cell Metab. 2016;24:9–10.

    CAS  PubMed  Google Scholar 

  57. 57.

    Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, Lefevre M, et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009;58:1509–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Kondo T, Kishi M, Fushimi T, Kaga T. Acetic acid upregulates the expression of genes for fatty acid oxidation enzymes in liver to suppress body fat accumulation. J Agric Food Chem. 2009;57:5982–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Aoki R, Kamikado K, Suda W, Takii H, Mikami Y, Suganuma N, et al. A proliferative probiotic Bifidobacterium strain in the gut ameliorates progression of metabolic disorders via microbiota modulation and acetate elevation. Sci Rep. 2017;7:43522.

    PubMed  PubMed Central  Google Scholar 

  60. 60.

    Hanatani S, Motoshima H, Takaki Y, Kawasaki S, Igata M, Matsumura T, et al. Acetate alters expression of genes involved in beige adipogenesis in 3T3-L1 cells and obese KK-Ay mice. J Clin Biochem Nutr. 2016;59:207–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Sahuri-Arisoylu M, Brody LP, Parkinson JR, Parkes H, Navaratnam N, Miller AD, et al. Reprogramming of hepatic fat accumulation and ‘browning’ of adipose tissue by the short-chain fatty acid acetate. Int J Obes. 2016;40:955–63.

    CAS  Google Scholar 

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This work was supported by the projects EPIMILK—AGL2012-33692— and INTERBIOBES —AGL2015-67019-P— (Agencia Estatal de Investigación, MINECO/FEDER, UE). FG-C was funded by the University of the Balearic Islands.

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FGC performed all the experimental procedures and co-wrote the first draft of the manuscript. BC and JN participated in the design and supervision of the in vitro experiments. CP participated in the design and discussion of the in vivo experiments. AD worked on the implementation of the technique for the analysis of SCFA in rat blood and in their measurement, and collaborated in the work with the animals. AMR and AP participated in all the experimental design and supervised it, together with the direct supervision of FGC and AD and the data generated. AMR co-wrote the first draft of the manuscript. AP suggested the main topic of study and directed the research grants of funding. All the authors revised and approved the final version of the manuscript.

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Correspondence to Ana María Rodríguez.

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The authors declare that they have no conflict of interest.

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These authors contributed equally: Ana María Rodríguez, Andreu Palou

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García-Carrizo, F., Cannon, B., Nedergaard, J. et al. Regulation of thermogenic capacity in brown and white adipocytes by the prebiotic high-esterified pectin and its postbiotic acetate. Int J Obes 44, 715–726 (2020).

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