Metabolic diseases caused by high-carbohydrate and/or high-salt diets are becoming major public health concerns. However, the effects of salt on high-carbohydrate diet-induced obesity are unclear. Accordingly, in this study, we investigated the effects of high-salt intake on high-carbohydrate diet-induced obesity.
We performed a 12-week study on gut microbiota and metabolic changes in high-rice diet (HRD) or HRD supplemented with high-salt (HRS)-fed C57BL/6 J mice by 16S rRNA analysis, glucose and insulin tolerance testing, gut barrier function, western blot and histological analysis. Moreover, the effects of salt on lipid metabolism were confirmed in vitro using 3T3-L1 cells.
High salt intake decreased HRD-induced increases in body and white adipose tissue (WAT) weight. Alternatively, HRS did not reverse the observed increases in glucose intolerance and insulin resistance. Moreover, HRD caused changes in the gut microbiota, thereby impairing gut barrier function and increasing inflammation in the liver. HRS altered HRD-induced microbial composition, however, did not ameliorate gut barrier dysfunction or hepatic inflammation. HRS diets regulated the HRD-induced increase in peroxisome proliferator-activated receptor-γ (PPAR-γ) and lipid metabolism-related protein expression. Moreover, within WAT, HRS was found to reverse the observed decrease in adiponectin and increase in PPAR-γ expression induced by HRD. In vitro, high NaCl concentration also significantly reduced 3T3-L1 cell differentiation and modulated lipid metabolism without causing cytotoxicity.
These results indicate that high salt intake ameliorates metabolic changes associated with a high-rice diet, including changes in fecal microbiota composition.
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Younossi Z, Tacke F, Arrese M, Sharma BC, Mostafa I, Bugianesi E, Wong VWS, Yilmaz Y, George J, Fan J (2019) Global perspectives on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Hepatology 69(6):2672–2682. https://doi.org/10.1002/hep.30251
Park S, Ahn J, Lee B-K (2016) Very-low-fat diets may be associated with increased risk of metabolic syndrome in the adult population. Clin Nutr 35(5):1159–1167. https://doi.org/10.1016/j.clnu.2015.09.010
Powles J, Fahimi S, Micha R, Khatibzadeh S, Shi P, Ezzati M, Engell RE, Lim SS, Danaei G, Mozaffarian D (2013) Global, regional and national sodium intakes in 1990 and 2010: a systematic analysis of 24 h urinary sodium excretion and dietary surveys worldwide. BMJ Open 3(12):e003733. https://doi.org/10.1136/bmjopen-2013-003733
Song S, Lee JE, Song WO, Paik H-Y, Song Y (2014) Carbohydrate intake and refined-grain consumption are associated with metabolic syndrome in the Korean adult population. J Acad Nutr Diet 114(1):54–62. https://doi.org/10.1016/j.jand.2013.08.025
Villegas R, Liu S, Gao Y-T, Yang G, Li H, Zheng W, Shu XO (2007) Prospective study of dietary carbohydrates, glycemic index, glycemic load, and incidence of type 2 diabetes mellitus in middle-aged Chinese women. Arch Intern Med 167(21):2310–2316. https://doi.org/10.1001/archinte.167.21.2310
Yu D, Shu X-O, Li H, Xiang Y-B, Yang G, Gao Y-T, Zheng W, Zhang X (2013) Dietary carbohydrates, refined grains, glycemic load, and risk of coronary heart disease in Chinese adults. Am J Epidemiol 178(10):1542–1549. https://doi.org/10.1093/aje/kwt178
Basaranoglu M, Basaranoglu G, Bugianesi E (2015) Carbohydrate intake and nonalcoholic fatty liver disease: fructose as a weapon of mass destruction. Hepatob Surg Nutr 4(2):109–116. https://doi.org/10.3978/j.issn.2304-3881.2014.11.05
Leibowitz A, Volkov A, Voloshin K, Shemesh C, Barshack I, Grossman E (2016) Melatonin prevents kidney injury in a high salt diet-induced hypertension model by decreasing oxidative stress. J Pineal Res 60(1):48–54. https://doi.org/10.1111/jpi.12287
Jiang L, Chen Q, Wu M, Ji T, Liu S, Zhu F, Shi D (2019) Short-term high salt intake impairs hepatic mitochondrial bioenergetics and biosynthesis in SIRT3 knockout mice. Free Radical Res 53(4):387–396. https://doi.org/10.1080/10715762.2019.1580499
Dornas WC, Cardoso LM, Silva M, Machado NL, Chianca-Jr DA, Alzamora AC, Lima WG, Lagente V, Silva ME (2017) Oxidative stress causes hypertension and activation of nuclear factor-κB after high-fructose and salt treatments. Sci Rep 7:46051. https://doi.org/10.1038/srep46051
Huang P, Shen Z, Liu J, Huang Y, Chen S, Yu W, Wang S, Ren Y, Li X, Tang C (2016) Hydrogen sulfide inhibits high-salt diet-induced renal oxidative stress and kidney injury in Dahl rats. Oxid Med Cell Longev. https://doi.org/10.1155/2016/2807490
Wang G, Yeung C-k, Wong W-Y, Zhang N, Wei Y-f, Zhang J-l, Yan Y, Wong C-y, Tang J-j, Chuai M (2016) Liver fibrosis can be induced by high salt intake through excess reactive oxygen species (ROS) production. J Agric Food Chem 64(7):1610–1617. https://doi.org/10.1021/acs.jafc.5b05897
Lanaspa MA, Kuwabara M, Andres-Hernando A, Li N, Cicerchi C, Jensen T, Orlicky DJ, Roncal-Jimenez CA, Ishimoto T, Nakagawa T (2018) High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism. Proc Natl Acad Sci 115(12):3138–3143. https://doi.org/10.1073/pnas.1713837115
Takagi Y, Sugimoto T, Kobayashi M, Shirai M, Asai F (2018) High-salt intake ameliorates hyperglycemia and insulin resistance in WBN/Kob-Leprfa/fa rats: a new model of type 2 diabetes mellitus. J Diabetes Res. https://doi.org/10.1155/2018/3671892
Pitynski-Miller D, Ross M, Schmill M, Schambow R, Fuller T, Flynn FW, Skinner DC (2017) A high salt diet inhibits obesity and delays puberty in the female rat. Int J Obes 41(11):1685–1692. https://doi.org/10.1038/ijo.2017.154
Huehnchen P, Boehmerle W, Endres M (2019) High salt diet ameliorates functional, electrophysiological and histological characteristics of murine spontaneous autoimmune polyneuropathy. Neurobiol Dis 124:240–247. https://doi.org/10.1016/j.nbd.2018.11.017
Wang L, Li P, Tang Z, Yan X, Feng B (2016) Structural modulation of the gut microbiota and the relationship with body weight: compared evaluation of liraglutide and saxagliptin treatment. Sci Rep 6:33251. https://doi.org/10.1038/srep33251
Boulangé CL, Neves AL, Chilloux J, Nicholson JK, Dumas M-E (2016) Impact of the gut microbiota on inflammation, obesity, and metabolic disease. Genome Med 8(1):42. https://doi.org/10.1186/s13073-016-0303-2
Li H, Limenitakis JP, Fuhrer T, Geuking MB, Lawson MA, Wyss M, Brugiroux S, Keller I, Macpherson JA, Rupp S (2015) The outer mucus layer hosts a distinct intestinal microbial niche. Nat Commun 6:8292. https://doi.org/10.1038/ncomms9292
Chen C, You LJ, Huang Q, Fu X, Zhang B, Liu RH, Li C (2018) Modulation of gut microbiota by mulberry fruit polysaccharide treatment of obese diabetic db/db mice. Food Funct 9(7):3732–3742. https://doi.org/10.1039/C7FO01346A
Kim W-G, Kim HI, Kwon EK, Han MJ, Kim D-H (2018) Lactobacillus plantarum LC27 and Bifidobacterium longum LC67 mitigate alcoholic steatosis in mice by inhibiting LPS-mediated NF-κB activation through restoration of the disturbed gut microbiota. Food Funct 9(8):4255–4265. https://doi.org/10.1039/C8FO00252E
Hamilton MK, Boudry G, Lemay DG, Raybould HE (2015) Changes in intestinal barrier function and gut microbiota in high-fat diet-fed rats are dynamic and region dependent. Am J Physiol Gastrointest Liver Physiol 308(10):840–851. https://doi.org/10.1152/ajpgi.00029.2015
Houghton D, Stewart C, Day C, Trenell M (2016) Gut microbiota and lifestyle interventions in NAFLD. Int J Mol Sci 17(4):447. https://doi.org/10.3390/ijms17040447
Clemente-Postigo M, Oliva-Olivera W, Coin-Aragüez L, Ramos-Molina B, Giraldez-Perez RM, Lhamyani S, Alcaide-Torres J, Perez-Martinez P, El Bekay R, Cardona F (2018) Metabolic endotoxemia promotes adipose dysfunction and inflammation in human obesity. Am J Physiol Endocrinol Metab 316(2):E319–E332. https://doi.org/10.1152/ajpendo.00277.2018
Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI (2007) Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci 104(3):979–984. https://doi.org/10.1073/pnas.0605374104
Cui H, Yang S, Zheng M, Liu R, Zhao G, Wen J (2017) High-salt intake negatively regulates fat deposition in mouse. Sci Rep 7(1):2053. https://doi.org/10.1038/s41598-017-01560-3
Magoč T, Salzberg SL (2011) FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics 27(21):2957–2963. https://doi.org/10.1093/bioinformatics/btr507
Cole JR, Wang Q, Fish JA, Chai B, McGarrell DM, Sun Y, Brown CT, Porras-Alfaro A, Kuske CR, Tiedje JM (2013) Ribosomal database project: data and tools for high throughput rRNA analysis. Nucleic Acids Res 42(D1):D633–D642. https://doi.org/10.1093/nar/gkt1244
Edgar RC (2010) Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26(19):2460–2461. https://doi.org/10.1093/bioinformatics/btq461
Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Pena AG, Goodrich JK, Gordon JI (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7(5):335–336. https://doi.org/10.1038/nmeth.f.303
Do M, Lee E, Oh M-J, Kim Y, Park H-Y (2018) High-glucose or-fructose diet cause changes of the gut microbiota and metabolic disorders in mice without body weight change. Nutrients 10(6):761. https://doi.org/10.3390/nu10060761
Yang T, Zollbrecht C, Winerdal ME, Zhuge Z, Zhang XM, Terrando N, Checa A, Sällström J, Wheelock CE, Winqvist O (2016) Genetic abrogation of adenosine A3 receptor prevents uninephrectomy and high salt–induced hypertension. J Am Heart Assoc 5(7):e003868. https://doi.org/10.1161/JAHA.116.003868
Spadaro PA, Naug HL, Du Toit EF, Donner D, Colson NJ (2015) A refined high carbohydrate diet is associated with changes in the serotonin pathway and visceral obesity. Genet Res. https://doi.org/10.1017/S0016672315000233
Flowers MT, Ntambi JM (2009) Stearoyl-CoA desaturase and its relation to high-carbohydrate diets and obesity. Biochim Biophys Acta 1791(2):85–91. https://doi.org/10.1016/j.bbalip.2008.12.011
Kirpich IA, Marsano LS, McClain CJ (2015) Gut–liver axis, nutrition, and non-alcoholic fatty liver disease. Clin Biochem 48(13–14):923–930. https://doi.org/10.1016/j.clinbiochem.2015.06.023
König J, Wells J, Cani PD, García-Ródenas CL, MacDonald T, Mercenier A, Whyte J, Troost F, Brummer R-J (2016) Human intestinal barrier function in health and disease. Clin Transl Gastroenterol 7(10):e196. https://doi.org/10.1038/ctg.2016.54
Zhang C, Zhang M, Pang X, Zhao Y, Wang L, Zhao L (2012) Structural resilience of the gut microbiota in adult mice under high-fat dietary perturbations. ISME J 6(10):1848. https://doi.org/10.1038/ismej.2012.27
Jang HM, Han SK, Kim JK, Oh SJ, Jang HB, Kim DH (2019) Lactobacillus sakei alleviates high-fat-diet-induced obesity and anxiety in mice by inducing AMPK activation and SIRT1 expression and inhibiting gut microbiota-mediated NF-κB activation. Mol Nutr Food Res 63(6):1800978. https://doi.org/10.1002/mnfr.201800978
Jeong M-Y, Jang H-M, Kim D-H (2019) High-fat diet causes psychiatric disorders in mice by increasing Proteobacteria population. Neurosci Lett 698:51–57. https://doi.org/10.1016/j.neulet.2019.01.006
Wang J, Tang H, Zhang C, Zhao Y, Derrien M, Rocher E, Vlieg JE, Strissel K, Zhao L, Obin M (2015) Modulation of gut microbiota during probiotic-mediated attenuation of metabolic syndrome in high fat diet-fed mice. ISME J 9(1):1–15. https://doi.org/10.1038/ismej.2014.99
Jiang W, Wu N, Wang X, Chi Y, Zhang Y, Qiu X, Hu Y, Li J, Liu Y (2015) Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease. Sci Rep 5:8096. https://doi.org/10.1038/srep08096
Araujo JR, Tomas J, Brenner C, Sansonetti PJ (2017) Impact of high-fat diet on the intestinal microbiota and small intestinal physiology before and after the onset of obesity. Biochimie 141:97–106. https://doi.org/10.1016/j.biochi.2017.05.019
Hersoug LG, Møller P, Loft S (2016) Gut microbiota-derived lipopolysaccharide uptake and trafficking to adipose tissue: implications for inflammation and obesity. Obes Rev 17(4):297–312. https://doi.org/10.1111/obr.12370
He M, Shi B (2017) Gut microbiota as a potential target of metabolic syndrome: the role of probiotics and prebiotics. Cell Biosci 7(1):54. https://doi.org/10.1186/s13578-017-0183-1
Rabot S, Membrez M, Bruneau A, Gérard P, Harach T, Moser M, Raymond F, Mansourian R, Chou CJ (2010) Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism. FASEB J 24(12):4948–4959. https://doi.org/10.1096/fj.10-164921
Yang Y, Zhong Z, Wang B, Xia X, Yao W, Huang L, Wang Y, Ding W (2019) Early-life high-fat diet-induced obesity programs hippocampal development and cognitive functions via regulation of gut commensal Akkermansia muciniphila. Neuropsychopharmacology 44(12):2054–2064. https://doi.org/10.1038/s41386-019-0437-1
Cani PD, Osto M, Geurts L, Everard A (2012) Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes 3(4):279–288. https://doi.org/10.4161/gmic.19625
Gäbele E, Dostert K, Hofmann C, Wiest R, Schölmerich J, Hellerbrand C, Obermeier F (2011) DSS induced colitis increases portal LPS levels and enhances hepatic inflammation and fibrogenesis in experimental NASH. J Hepatol 55(6):1391–1399. https://doi.org/10.1016/j.jhep.2011.02.035
Gavrilova O, Haluzik M, Matsusue K, Cutson JJ, Johnson L, Dietz KR, Nicol CJ, Vinson C, Gonzalez FJ, Reitman ML (2003) Liver peroxisome proliferator-activated receptor γ contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass. J Biol Chem 278(36):34268–34276. https://doi.org/10.1074/jbc.M300043200
Zhang Y, Fan S, Hu N, Gu M, Chu C, Li Y, Lu X, Huang C (2012) Rhein reduces fat weight in db/db mouse and prevents diet-induced obesity in C57Bl/6 mouse through the inhibition of PPARγ signaling. PPAR Res. https://doi.org/10.1155/2012/374936
García-Mediavilla MV, Pisonero-Vaquero S, Lima-Cabello E, Benedicto I, Majano PL, Jorquera F, González-Gallego J, Sánchez-Campos S (2012) Liver X receptor α-mediated regulation of lipogenesis by core and NS5A proteins contributes to HCV-induced liver steatosis and HCV replication. Lab Invest 92(8):1191. https://doi.org/10.1038/labinvest.2012.88
Wein S, Behm N, Petersen RK, Kristiansen K, Wolffram S (2010) Quercetin enhances adiponectin secretion by a PPAR-γ independent mechanism. Eur J Pharm Sci 41(1):16–22. https://doi.org/10.1016/j.ejps.2010.05.004
Achari A, Jain S (2017) Adiponectin, a therapeutic target for obesity, diabetes, and endothelial dysfunction. Int J Mol Sci 18(6):1321. https://doi.org/10.3390/ijms18061321
Pettinelli P, Videla LA (2011) Up-regulation of PPAR-γ mRNA expression in the liver of obese patients: an additional reinforcing lipogenic mechanism to SREBP-1c induction. J Clin Endocrinol Metabol 96(5):1424–1430. https://doi.org/10.1210/jc.2010-2129
This research was supported by the Main Research Program (E0170602-03) of the Korea Food Research Institute (KFRI) funded by the Ministry of Science and ICT.
The authors declare that they have no competing interests.
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Do, M.H., Lee, HB., Oh, MJ. et al. Consumption of salt leads to ameliorate symptoms of metabolic disorder and change of gut microbiota. Eur J Nutr 59, 3779–3790 (2020). https://doi.org/10.1007/s00394-020-02209-0
- High-salt diet
- High-rice diet
- Metabolic disorder
- Lipid metabolism