Eubacterium siraeum suppresses fat deposition via decreasing the tyrosine-mediated PI3K/AKT signaling pathway in high-fat diet-induced obesity.
Eubacterium siraeum
Laiwu pig
Lulai black pig
Fat deposition
Journal
Microbiome
ISSN: 2049-2618
Titre abrégé: Microbiome
Pays: England
ID NLM: 101615147
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
received:
02
07
2024
accepted:
04
10
2024
medline:
31
10
2024
pubmed:
31
10
2024
entrez:
31
10
2024
Statut:
epublish
Résumé
Obesity in humans can lead to chronic diseases such as diabetes and cardiovascular disease. Similarly, subcutaneous fat (SCF) in pigs affects feed utilization, and excessive SCF can reduce the feed efficiency of pigs. Therefore, identifying factors that suppress fat deposition is particularly important. Numerous studies have implicated the gut microbiome in pigs' fat deposition, but research into its suppression remains scarce. The Lulai black pig (LL) is a hybrid breed derived from the Laiwu pig (LW) and the Yorkshire pig, with lower levels of SCF compared to the LW. In this study, we focused on these breeds to identify microbiota that regulate fat deposition. The key questions were: Which microbial populations reduce fat in LL pigs compared to LW pigs, and what is the underlying regulatory mechanism? In this study, we identified four different microbial strains, Eubacterium siraeum, Treponema bryantii, Clostridium sp. CAG:413, and Jeotgalibaca dankookensis, prevalent in both LW and LL pigs. Blood metabolome analysis revealed 49 differential metabolites, including tanshinone IIA and royal jelly acid, known for their anti-adipogenic properties. E. siraeum was strongly correlated with these metabolites, and its genes and metabolites were enriched in pathways linked to fatty acid degradation, glycerophospholipid, and glycerolipid metabolism. In vivo mouse experiments confirmed that E. siraeum metabolites curb weight gain, reduce SCF adipocyte size, increase the number of brown adipocytes, and regulate leptin, IL-6, and insulin secretion. Finally, we found that one important pathway through which E. siraeum inhibits fat deposition is by suppressing the phosphorylation of key proteins in the PI3K/AKT signaling pathway through the reduction of tyrosine. We compared LW and LL pigs using fecal metagenomics, metabolomics, and blood metabolomics, identifying E. siraeum as a strain linked to fat deposition. Oral administration experiments in mice demonstrated that E. siraeum effectively inhibits fat accumulation, primarily through the suppression of the PI3K/AKT signaling pathway, a critical regulator of lipid metabolism. These findings provide a valuable theoretical basis for improving pork quality and offer insights relevant to the study of human obesity and related chronic metabolic diseases. Video Abstract.
Sections du résumé
BACKGROUND
BACKGROUND
Obesity in humans can lead to chronic diseases such as diabetes and cardiovascular disease. Similarly, subcutaneous fat (SCF) in pigs affects feed utilization, and excessive SCF can reduce the feed efficiency of pigs. Therefore, identifying factors that suppress fat deposition is particularly important. Numerous studies have implicated the gut microbiome in pigs' fat deposition, but research into its suppression remains scarce. The Lulai black pig (LL) is a hybrid breed derived from the Laiwu pig (LW) and the Yorkshire pig, with lower levels of SCF compared to the LW. In this study, we focused on these breeds to identify microbiota that regulate fat deposition. The key questions were: Which microbial populations reduce fat in LL pigs compared to LW pigs, and what is the underlying regulatory mechanism?
RESULTS
RESULTS
In this study, we identified four different microbial strains, Eubacterium siraeum, Treponema bryantii, Clostridium sp. CAG:413, and Jeotgalibaca dankookensis, prevalent in both LW and LL pigs. Blood metabolome analysis revealed 49 differential metabolites, including tanshinone IIA and royal jelly acid, known for their anti-adipogenic properties. E. siraeum was strongly correlated with these metabolites, and its genes and metabolites were enriched in pathways linked to fatty acid degradation, glycerophospholipid, and glycerolipid metabolism. In vivo mouse experiments confirmed that E. siraeum metabolites curb weight gain, reduce SCF adipocyte size, increase the number of brown adipocytes, and regulate leptin, IL-6, and insulin secretion. Finally, we found that one important pathway through which E. siraeum inhibits fat deposition is by suppressing the phosphorylation of key proteins in the PI3K/AKT signaling pathway through the reduction of tyrosine.
CONCLUSIONS
CONCLUSIONS
We compared LW and LL pigs using fecal metagenomics, metabolomics, and blood metabolomics, identifying E. siraeum as a strain linked to fat deposition. Oral administration experiments in mice demonstrated that E. siraeum effectively inhibits fat accumulation, primarily through the suppression of the PI3K/AKT signaling pathway, a critical regulator of lipid metabolism. These findings provide a valuable theoretical basis for improving pork quality and offer insights relevant to the study of human obesity and related chronic metabolic diseases. Video Abstract.
Identifiants
pubmed: 39478562
doi: 10.1186/s40168-024-01944-4
pii: 10.1186/s40168-024-01944-4
doi:
Substances chimiques
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
223Informations de copyright
© 2024. The Author(s).
Références
Fernandez X, Monin G, Talmant A, Mourot J, Lebret B. Influence of intramuscular fat content on the quality of pig meat - 1. Composition of the lipid fraction and sensory characteristics of m. longissimus lumborum. Meat Sci. 1999;53(1):59–65.
pubmed: 22062933
doi: 10.1016/S0309-1740(99)00037-6
Zhou G, Wang S, Wang Z, Zhu X, Shu G, Liao W, Yu K, Gao P, Xi Q, Wang X, et al. Global comparison of gene expression profiles between intramuscular and subcutaneous adipocytes of neonatal landrace pig using microarray. Meat Sci. 2010;86(2):440–50.
pubmed: 20573458
doi: 10.1016/j.meatsci.2010.05.031
Pi-Sunyer FX. The obesity epidemic: pathophysiology and consequences of obesity. Obes Res. 2002;10(Suppl 2):97s–104s.
pubmed: 12490658
Sullivan PW, Ghushchyan VH, Ben-Joseph R. The impact of obesity on diabetes, hyperlipidemia and hypertension in the United States. Qual Life Res. 2008;17(8):1063–71.
pubmed: 18777200
doi: 10.1007/s11136-008-9385-7
Khan MT, Nieuwdorp M, Bäckhed F. Microbial modulation of insulin sensitivity. Cell Metab. 2014;20(5):753–60.
pubmed: 25176147
doi: 10.1016/j.cmet.2014.07.006
Xiong X, Liu X, Zhou L, Yang J, Yang B, Ma H, Xie X, Huang Y, Fang S, Xiao S, et al. Genome-wide association analysis reveals genetic loci and candidate genes for meat quality traits in Chinese Laiwu pigs. Mamm Genome. 2015;26(3–4):181–90.
pubmed: 25678226
doi: 10.1007/s00335-015-9558-y
Qiao R, Gao J, Zhang Z, Li L, Xie X, Fan Y, Cui L, Ma J, Ai H, Ren J, et al. Genome-wide association analyses reveal significant loci and strong candidate genes for growth and fatness traits in two pig populations. Genet Sel Evol. 2015;47(1):17.
pubmed: 25885760
pmcid: 4358731
doi: 10.1186/s12711-015-0089-5
Guo Y, Qiu H, Xiao S, Wu Z, Yang M, Yang J, Ren J, Huang L. A genome-wide association study identifies genomic loci associated with backfat thickness, carcass weight, and body weight in two commercial pig populations. J Appl Genet. 2017;58(4):499–508.
pubmed: 28890999
doi: 10.1007/s13353-017-0405-6
Cho IC, Park HB, Ahn JS, Han SH, Lee JB, Lim HT, Yoo CK, Jung EJ, Kim DH, Sun WS, et al. A functional regulatory variant of MYH3 influences muscle fiber-type composition and intramuscular fat content in pigs. PLoS Genet. 2019;15(10): e1008279.
pubmed: 31603892
pmcid: 6788688
doi: 10.1371/journal.pgen.1008279
Zilber-Rosenberg I, Rosenberg E. Role of microorganisms in the evolution of animals and plants: the hologenome theory of evolution. FEMS Microbiol Rev. 2008;32(5):723–35.
pubmed: 18549407
doi: 10.1111/j.1574-6976.2008.00123.x
Yan H, Diao H, Xiao Y, Li W, Yu B, He J, Yu J, Zheng P, Mao X, Luo Y, et al. Gut microbiota can transfer fiber characteristics and lipid metabolic profiles of skeletal muscle from pigs to germ-free mice. Sci Rep. 2016;6: 31786.
pubmed: 27545196
pmcid: 4992887
doi: 10.1038/srep31786
Ma J, Duan Y, Li R, Liang X, Li T, Huang X, Yin Y, Yin J. Gut microbial profiles and the role in lipid metabolism in Shaziling pigs. Anim Nutr. 2022;9:345–56.
pubmed: 35600540
pmcid: 9111993
doi: 10.1016/j.aninu.2021.10.012
Chen C, Fang S, Wei H, He M, Fu H, Xiong X, Zhou Y, Wu J, Gao J, Yang H, et al. Prevotella copri increases fat accumulation in pigs fed with formula diets. Microbiome. 2021;9(1):175.
pubmed: 34419147
pmcid: 8380364
doi: 10.1186/s40168-021-01110-0
Krautkramer KA, Fan J, Bäckhed F. Gut microbial metabolites as multi-kingdom intermediates. Nat Rev Microbiol. 2021;19(2):77–94.
pubmed: 32968241
doi: 10.1038/s41579-020-0438-4
Li X, Shimizu Y, Kimura I. Gut microbial metabolite short-chain fatty acids and obesity. Biosci Microbiota Food Health. 2017;36(4):135–40.
pubmed: 29038768
pmcid: 5633527
doi: 10.12938/bmfh.17-010
Lai X, Zhang Z, Zhang Z, Liu S, Bai C, Chen Z, Qadri QR, Fang Y, Wang Z, Pan Y, et al. Integrated microbiome-metabolome-genome axis data of Laiwu and Lulai pigs. Sci Data. 2023;10(1):280.
pubmed: 37179393
pmcid: 10183000
doi: 10.1038/s41597-023-02191-2
Cao R, Feng J, Xu Y, Fang Y, Zhao W, Zhang Z, Zhang Z, Li M, Wang Q, Pan Y. Genomic signatures reveal breeding effects of Lulai pigs. Genes (Basel). 2022;13(11):1969.
pubmed: 36360207
doi: 10.3390/genes13111969
Chen QM, Wang H, Zeng YQ, Chen W. Developmental changes and effect on intramuscular fat content of H-FABP and A-FABP mRNA expression in pigs. J Appl Genet. 2013;54(1):119–23.
pubmed: 23135696
doi: 10.1007/s13353-012-0122-0
Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15):2114–20.
pubmed: 24695404
doi: 10.1093/bioinformatics/btu170
Li H, Durbin R. Fast and accurate short read alignment with burrows-wheeler transform. Bioinformatics. 2009;25(14):1754–60.
pubmed: 19451168
pmcid: 2705234
doi: 10.1093/bioinformatics/btp324
Peng Y, Leung HC, Yiu SM, Chin FY. IDBA-UD: a de novo assembler for single-cell and metagenomic sequencing data with highly uneven depth. Bioinformatics. 2012;28(11):1420–8.
pubmed: 22495754
doi: 10.1093/bioinformatics/bts174
Zhu W, Lomsadze A, Borodovsky M. Ab initio gene identification in metagenomic sequences. Nucleic Acids Res. 2010;38(12): e132.
pubmed: 20403810
pmcid: 2896542
doi: 10.1093/nar/gkq275
Li W, Godzik A. Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics. 2006;22(13):1658–9.
pubmed: 16731699
doi: 10.1093/bioinformatics/btl158
Gu S, Fang L, Xu X. Using SOAPaligner for Short Reads Alignment. Curr Protoc Bioinform. 2013;44:11 .11.11-17.
doi: 10.1002/0471250953.bi1111s44
Galperin MY, Kristensen DM, Makarova KS, Wolf YI, Koonin EV. Microbial genome analysis: the COG approach. Brief Bioinform. 2019;20(4):1063–70.
pubmed: 28968633
doi: 10.1093/bib/bbx117
Iastrebova OV. Functioning of fructose-1,6-bisphosphatase–main enzyme of gluconeogenesis in microorganisms. Ukr Biokhim Zh (1999). 2002;74(4):24–32.
pubmed: 14964858
Legouis D, Faivre A, Cippà PE, de Seigneux S. Renal gluconeogenesis: an underestimated role of the kidney in systemic glucose metabolism. Nephrol Dial Transplant. 2022;37(8):1417–25.
pubmed: 33247734
doi: 10.1093/ndt/gfaa302
Russell TR, Demeler B, Tu SC. Kinetic mechanism and quaternary structure of Aminobacter aminovorans NADH:flavin oxidoreductase: an unusual flavin reductase with bound flavin. Biochemistry. 2004;43(6):1580–90.
pubmed: 14769034
doi: 10.1021/bi035578a
Sáenz de Urturi D, Buqué X, Porteiro B, Folgueira C, Mora A, Delgado TC, Prieto-Fernández E, Olaizola P, Gómez-Santos B, Apodaka-Biguri M, et al. Methionine adenosyltransferase 1a antisense oligonucleotides activate the liver-brown adipose tissue axis preventing obesity and associated hepatosteatosis. Nat Commun. 2022;13(1):1096.
pubmed: 35232994
pmcid: 8888704
doi: 10.1038/s41467-022-28749-z
Isidor MS, Winther S, Markussen LK, Basse AL, Quistorff B, Nedergaard J, Emanuelli B, Hansen JB. Pyruvate kinase M2 represses thermogenic gene expression in brown adipocytes. FEBS Lett. 2020;594(7):1218–25.
pubmed: 31823361
doi: 10.1002/1873-3468.13716
Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027–31.
pubmed: 17183312
doi: 10.1038/nature05414
Sonnenburg JL, Bäckhed F. Diet-microbiota interactions as moderators of human metabolism. Nature. 2016;535(7610):56–64.
pubmed: 27383980
doi: 10.1038/nature18846
Festi D, Schiumerini R, Eusebi LH, Marasco G, Taddia M, Colecchia A. Gut microbiota and metabolic syndrome. World J Gastroenterol. 2014;20(43):16079–94.
pubmed: 25473159
doi: 10.3748/wjg.v20.i43.16079
Toniolo P, Van Kappel AL, Akhmedkhanov A, Ferrari P, Kato I, Shore RE, Riboli E. Serum carotenoids and breast cancer. Am J Epidemiol. 2001;153(12):1142–7.
pubmed: 11415946
doi: 10.1093/aje/153.12.1142
Shimode S, Miyata K, Araki M, Shindo K. Antioxidant activities of the antheraxanthin-related carotenoids, antheraxanthin, 9-cis-antheraxanthin, and mutatoxanthins. J Oleo Sci. 2018;67(8):977–81.
pubmed: 30068828
doi: 10.5650/jos.ess18060
Swargiary G, Mani S. Molecular docking and simulation studies of phytocompounds derived from centella asiatica and andrographis paniculata against hexokinase II as mitocan agents. Mitochondrion. 2021;61:138–46.
pubmed: 34606995
doi: 10.1016/j.mito.2021.09.013
Daood HG, Palotás G, Palotás G, Somogyi G, Pék Z, Helyes L. Carotenoid and antioxidant content of ground paprika from indoor-cultivated traditional varieties and new hybrids of spice red peppers. Food Res Int. 2014;65:231–7.
doi: 10.1016/j.foodres.2014.04.048
Shen MC, Zhao X, Siegal GP, Desmond R, Hardy RW. Dietary stearic acid leads to a reduction of visceral adipose tissue in athymic nude mice. PLoS ONE. 2014;9(9): e104083.
pubmed: 25222131
doi: 10.1371/journal.pone.0104083
Yoneshiro T, Kaede R, Nagaya K, Aoyama J, Saito M, Okamatsu-Ogura Y, Kimura K, Terao A. Royal jelly ameliorates diet-induced obesity and glucose intolerance by promoting brown adipose tissue thermogenesis in mice. Obes Res Clin Pract. 2018;12(Suppl 2):127–37.
pubmed: 28089395
doi: 10.1016/j.orcp.2016.12.006
Irandoost P, Mesri Alamdari N, Saidpour A, Shidfar F, Roshanravan N, Asghari Jafarabadi M, Farsi F, Asghari Hanjani N, Vafa M. The effects of royal jelly and tocotrienol-rich fraction on impaired glycemic control and inflammation through irisin in obese rats. J Food Biochem. 2020;44(12): e13493.
pubmed: 33020956
doi: 10.1111/jfbc.13493
Keppley LJW, Walker SJ, Gademsey AN, Smith JP, Keller SR, Kester M, Fox TE. Nervonic acid limits weight gain in a mouse model of diet-induced obesity. Faseb j. 2020;34(11):15314–26.
pubmed: 32959931
doi: 10.1096/fj.202000525R
Park YK, Obiang-Obounou BW, Lee J, Lee TY, Bae MA, Hwang KS, Lee KB, Choi JS, Jang BC. Anti-Adipogenic Effects on 3T3-L1 Cells and Zebrafish by Tanshinone IIA. Int J Mol Sci. 2017;18(10):2065.
pubmed: 28953247
pmcid: 5666747
doi: 10.3390/ijms18102065
Raz I, Eldor R, Cernea S, Shafrir E. Diabetes: insulin resistance and derangements in lipid metabolism. Cure through intervention in fat transport and storage. Diabetes Metab Res Rev. 2005;21(1):3–14.
pubmed: 15386813
doi: 10.1002/dmrr.493
Martínez-Sánchez N. There and back again: leptin actions in white adipose tissue. Int J Mol Sci. 2020;21(17):6039.
pubmed: 32839413
pmcid: 7503240
doi: 10.3390/ijms21176039
Trayhurn P. Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr. 2022;127(2):161–4.
pubmed: 35016740
doi: 10.1017/S0007114521003962
Dang TTH, Yun JW. Cytochrome P450 2E1 (CYP2E1) positively regulates lipid catabolism and induces browning in 3T3-L1 white adipocytes. Life Sci. 2021;278: 119648.
pubmed: 34043994
doi: 10.1016/j.lfs.2021.119648
Abdelmegeed MA, Choi Y, Godlewski G, Ha SK, Banerjee A, Jang S, Song BJ. Cytochrome P450–2E1 promotes fast food-mediated hepatic fibrosis. Sci Rep. 2017;7: 39764.
pubmed: 28051126
pmcid: 5209674
doi: 10.1038/srep39764
Nguyen Huu T, Park J, Zhang Y, Park I, Yoon HJ, Woo HA, Lee SR. Redox Regulation of PTEN by Peroxiredoxins. Antioxidants (Basel). 2021;10(2):302.
pubmed: 33669370
doi: 10.3390/antiox10020302
Chiarugi P, Cirri P. Redox regulation of protein tyrosine phosphatases during receptor tyrosine kinase signal transduction. Trends Biochem Sci. 2003;28(9):509–14.
pubmed: 13678963
doi: 10.1016/S0968-0004(03)00174-9
Yin Y, Huang X, Lynn KD, Thorpe PE. Phosphatidylserine-targeting antibody induces M1 macrophage polarization and promotes myeloid-derived suppressor cell differentiation. Cancer Immunol Res. 2013;1(4):256–68.
pubmed: 24777853
doi: 10.1158/2326-6066.CIR-13-0073
Dai W, Zhang J, Chen L, Yu J, Zhang J, Yin H, Shang Q, Yu G. Discovery of Bacteroides uniformis F18–22 as a Safe and Novel Probiotic Bacterium for the Treatment of Ulcerative Colitis from the Healthy Human Colon. Int J Mol Sci. 2023;24(19):14669.
pubmed: 37834117
pmcid: 10572632
doi: 10.3390/ijms241914669
Qiao X, Gao Y, Li J, Wang Z, Qiao H, Qi H. Sensitive analysis of single nucleotide variation by Cas13d orthologs, EsCas13d and RspCas13d. Biotechnol Bioeng. 2021;118(8):3037–45.
pubmed: 33964175
doi: 10.1002/bit.27813
Wang Y, Wang Y, Tang N, Wang Z, Pan D, Ji Q. Characterization and engineering of a novel miniature eubacterium siraeum CRISPR-Cas12f System. ACS Synth Biol. 2024;13(7):2115–27.
pubmed: 38941613
doi: 10.1021/acssynbio.4c00154
Yan WX, Chong S, Zhang H, Makarova KS, Koonin EV, Cheng DR, Scott DA. Cas13d Is a compact RNA-targeting Type VI CRISPR effector positively modulated by a WYL-domain-containing accessory protein. Mol Cell. 2018;70(2):327-339.e325.
pubmed: 29551514
pmcid: 5935466
doi: 10.1016/j.molcel.2018.02.028
Hu X, Yu C, He Y, Zhu S, Wang S, Xu Z, You S, Jiao Y, Liu SL, Bao H. Integrative metagenomic analysis reveals distinct gut microbial signatures related to obesity. BMC Microbiol. 2024;24(1):119.
pubmed: 38580930
pmcid: 10996249
doi: 10.1186/s12866-024-03278-5
Newman TM, Shively CA, Register TC, Appt SE, Yadav H, Colwell RR, Fanelli B, Dadlani M, Graubics K, Nguyen UT, et al. Diet, obesity, and the gut microbiome as determinants modulating metabolic outcomes in a non-human primate model. Microbiome. 2021;9(1):100.
pubmed: 33952353
pmcid: 8101030
doi: 10.1186/s40168-021-01069-y
Ye D, Huang J, Wu J, Xie K, Gao X, Yan K, Zhang P, Tao Y, Li Y, Zang S, et al. Integrative metagenomic and metabolomic analyses reveal gut microbiota-derived multiple hits connected to development of gestational diabetes mellitus in humans. Gut Microbes. 2023;15(1): 2154552.
pubmed: 36550785
doi: 10.1080/19490976.2022.2154552
Wang M, Xu X, Sheng M, Zhang M, Wu F, Zhao Z, Guo M, Fang B, Wu J. Tannic acid protects against colitis by regulating the IL17 - NFκB and microbiota - methylation pathways. Int J Biol Macromol. 2024;274(Pt 1): 133334.
pubmed: 38908626
doi: 10.1016/j.ijbiomac.2024.133334
Zhao N, Ma Y, Liang X, Zhang Y, Hong D, Wang Y, Bai D. Efficacy and Mechanism of Qianshan Huoxue Gao in Acute Coronary Syndrome via Regulation of Intestinal Flora and Metabolites. Drug Des Devel Ther. 2023;17:579–95.
pubmed: 36855515
pmcid: 9968440
doi: 10.2147/DDDT.S396649
Zhu Z, Hu C, Liu Y, Wang F, Zhu B. Inulin has a beneficial effect by modulating the intestinal microbiome in a BALB/c mouse model. Benef Microbes. 2023;14(4):371–83.
pubmed: 38661353
doi: 10.1163/18762891-20220094
He J, Zhang P, Shen L, Niu L, Tan Y, Chen L, Zhao Y, Bai L, Hao X, Li X, et al. Short-chain fatty acids and their association with signalling pathways in inflammation, glucose and lipid metabolism. Int J Mol Sci. 2020;21(17):6356.
pubmed: 32887215
pmcid: 7503625
doi: 10.3390/ijms21176356
den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013;54(9):2325–40.
doi: 10.1194/jlr.R036012
Du J, Zhang P, Luo J, Shen L, Zhang S, Gu H, He J, Wang L, Zhao X, Gan M, et al. Dietary betaine prevents obesity through gut microbiota-drived microRNA-378a family. Gut Microbes. 2021;13(1):1–19.
pubmed: 33550882
doi: 10.1080/19490976.2020.1862612
Sahuri-Arisoylu M, Brody LP, Parkinson JR, Parkes H, Navaratnam N, Miller AD, Thomas EL, Frost G, Bell JD. Reprogramming of hepatic fat accumulation and “browning” of adipose tissue by the short-chain fatty acid acetate. Int J Obes (Lond). 2016;40(6):955–63.
pubmed: 26975441
doi: 10.1038/ijo.2016.23
Ye RZ, Richard G, Gévry N, Tchernof A, Carpentier AC. Fat cell size: measurement methods, pathophysiological origins, and relationships with metabolic dysregulations. Endocr Rev. 2022;43(1):35–60.
pubmed: 34100954
doi: 10.1210/endrev/bnab018
Ikeda K, Yamada T. UCP1 dependent and independent thermogenesis in brown and beige adipocytes. Front Endocrinol (Lausanne). 2020;11:498.
pubmed: 32849287
doi: 10.3389/fendo.2020.00498
Viladomiu M, Hontecillas R, Bassaganya-Riera J. Modulation of inflammation and immunity by dietary conjugated linoleic acid. Eur J Pharmacol. 2016;785:87–95.
pubmed: 25987426
doi: 10.1016/j.ejphar.2015.03.095
Muhammad I, Luo W, Shoaib RM, Li GL, Shams Ul Hassan S, Yang ZH, Xiao X, Tu GL, Yan SK, Ma XP, et al. Guaiane-type sesquiterpenoids from Cinnamomum migao H. W. Li: And their anti-inflammatory activities. Phytochemistry. 2021;190: 112850.
pubmed: 34217042
doi: 10.1016/j.phytochem.2021.112850
Li HM, Fan M, Xue Y, Peng LY, Wu XD, Liu D, Li RT, Zhao QS. Guaiane-Type Sesquiterpenoids from Alismatis Rhizoma and Their Anti-inflammatory Activity. Chem Pharm Bull (Tokyo). 2017;65(4):403–7.
pubmed: 28381681
doi: 10.1248/cpb.c16-00798
Guo R, Duan ZK, Li Q, Yao GD, Song SJ, Huang XX. Guide isolation of guaiane-type sesquiterpenoids from Daphne tangutica maxim. And their anti-inflammatory activities. Phytochemistry. 2023;206:113523.
pubmed: 36442577
doi: 10.1016/j.phytochem.2022.113523
Matsubara K, Matsuzawa Y, Jiao S, Kihara S, Takama T, Nakamura T, Tokunaga K, Kubo M, Tarui S. Cholesterol-lowering effect of N-(alpha-methylbenzyl)linoleamide (melinamide) in cholesterol-fed diabetic rats. Atherosclerosis. 1988;72(2–3):199–204.
pubmed: 3214468
doi: 10.1016/0021-9150(88)90081-0
Nakajima T, Natori K, Hirohashi T, Aono S. Inhibitory effect of melinamide on cholesterol solubility in mixed micellar solution of sodium taurocholate. Chem Pharm Bull (Tokyo). 1986;34(10):4273–9.
pubmed: 3829159
doi: 10.1248/cpb.34.4273
Barcenilla A, Pryde SE, Martin JC, Duncan SH, Stewart CS, Henderson C, Flint HJ. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl Environ Microbiol. 2000;66(4):1654–61.
pubmed: 10742256
pmcid: 92037
doi: 10.1128/AEM.66.4.1654-1661.2000
Louis P, Flint HJ. Formation of propionate and butyrate by the human colonic microbiota. Environ Microbiol. 2017;19(1):29–41.
pubmed: 27928878
doi: 10.1111/1462-2920.13589
Turroni S, Rampelli S, Biagi E, Consolandi C, Severgnini M, Peano C, Quercia S, Soverini M, Carbonero FG, Bianconi G, et al. Temporal dynamics of the gut microbiota in people sharing a confined environment, a 520-day ground-based space simulation, MARS500. Microbiome. 2017;5(1):39.
pubmed: 28340597
doi: 10.1186/s40168-017-0256-8
Inoki K, Li Y, Zhu T, Wu J, Guan KL. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol. 2002;4(9):648–57.
pubmed: 12172553
doi: 10.1038/ncb839
Degirmenci U, Wang M, Hu J. Targeting Aberrant RAS/RAF/MEK/ERK Signaling for Cancer Therapy. Cells. 2020;9(1):198.
pubmed: 31941155
doi: 10.3390/cells9010198
Savova MS, Mihaylova LV, Tews D, Wabitsch M, Georgiev MI. Targeting PI3K/AKT signaling pathway in obesity. Biomed Pharmacother. 2023;159: 114244.
pubmed: 36638594
doi: 10.1016/j.biopha.2023.114244
Feng H, Liu T, Yousuf S, Zhang X, Huang W, Li A, Xie L, Miao X. Identification and analysis of lncRNA, miRNA and mRNA related to subcutaneous and intramuscular fat in Laiwu pigs. Front Endocrinol (Lausanne). 2022;13:1081460.
pubmed: 36714570
doi: 10.3389/fendo.2022.1081460
Feng H, Yousuf S, Liu T, Zhang X, Huang W, Li A, Xie L, Miao X. The comprehensive detection of miRNA and circRNA in the regulation of intramuscular and subcutaneous adipose tissue of Laiwu pig. Sci Rep. 2022;12(1):16542.
pubmed: 36192451
pmcid: 9530237
doi: 10.1038/s41598-022-21045-2
Feng H, Liu TY, Salsabeel Y, Miao XY. Transcriptome analysis of intramuscular and subcutaneous fat of Laiwu pig. Life Sci Res. 2023;27(02):179–88.