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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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.
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.
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.
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.
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.
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.
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.
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.
Galanakis CM. Nutraceutical and functional food components: effects of innovative processing techniques. London, UK: Academic Press; 2017. p. 1.
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.
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.
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.
Nedergaard J, Cannon B. The browning of white adipose tissue: some burning issues. Cell Metab. 2014;20:396–407.
Palou A, Pico C, Bonet ML, Oliver P. The uncoupling protein, thermogenin. Int J Biochem Cell Biol. 1998;30:7–11.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Koleva PT, Bridgman SL, Kozyrskyj AL. The infant gut microbiome: evidence for obesity risk and dietary intervention. Nutrients. 2015;7:2237–60.
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.
Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, et al. Host-gut microbiota metabolic interactions. Science. 2012;336:1262–7.
Jakobsdottir G, Nyman M, Fåk F. Designing future prebiotic fiber to target the metabolic syndrome. Nutrition. 2014;30:497–502.
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.
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.
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.
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.
Townsend KL, Tseng Y-HH. Brown fat fuel utilization and thermogenesis. Trends Endocrinol Metab. 2014;25:168–77.
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.
Kalinovich AV, de Jong JM, Cannon B, Nedergaard J. UCP1 in adipose tissues: two steps to full browning. Biochimie. 2017;134:127–37.
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.
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.
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.
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.
Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84:277–59.
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.
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.
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.
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.
Slavin J. Fiber and prebiotics: mechanisms and health benefits. Nutrients. 2013;5:1417–35.
Bonet ML, Oliver P, Palou A. Pharmacological and nutritional agents promoting browning of white adipose tissue. Biochim et Biophys acta. 2013;1831:969–85.
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.
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.
Reynes B, Palou M, Rodriguez AM, Palou A. Regulation of adaptive thermogenesis and browning by prebiotics and postbiotics. Front Physiol. 2018;9:1908.
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.
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.
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.
Rosenwald M, Perdikari A, Rülicke T, Wolfrum C. Bi-directional interconversion of brite and white adipocytes. Nat Cell Biol. 2013;15:659–67.
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.
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.
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.
Trent CM, Blaser MJ. Microbially produced acetate: a "missing link" in understanding obesity? Cell Metab. 2016;24:9–10.
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.
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.
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.
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.
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.
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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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). https://doi.org/10.1038/s41366-019-0445-6