Dietary adenosine 5’-monophosphate supplementation increases food intake and remodels energy expenditure in mice
Abstract
Background: Dietary nucleotides [inclusion adenosine 5’-monophosphate (AMP)] supplementation was shown to promote the feed intake of sows and increase the AMP content in their milk in our previous work, but whether AMP shapes the energy expenditure and lipid metabolism in mammals remains unknown. Here, we aimed to explore the effects and the related mechanism of dietary AMP supplementation on food intake, body composition, energy expenditure, and lipid metabolism in male mice.
Methods: 4-week-old C57BL/6 mice (After a 1-wk adaptation) were fed with basal diet and basal diet supplemented with 0.1% AMP, respectively. Animal food intake and body weight were monitored and after 4 weeks all animals were sacrificed to measure the body composition, energy expenditure and lipid metabolism changes.
Results: Compared with the control, the 0.1% AMP fed mice showed higher food intake while lower adipose weight. Intriguingly, dietary AMP supplementation was found to stimulate brown adipose tissue thermogenesis as evidenced by the increase in the uncoupling protein-1 level and the core temperature. Moreover, AMP supplementation was shown to promote white adipose tissue lipolysis as indicated by smaller lipid droplet size in mice. These results demonstrate that dietary AMP supplementation could enhance oxygen consumption and energy expenditure.
Conclusions: This study highlights the physiological importance of AMP supplementation in mediating food intake and energy expenditure and suggests its potential as an adjuvant therapy in preventing energy metabolic disorders (mainly obesity and diabetes).
Downloads
References
- Malik VS, Willet WC, Hu FB. Nearly a decade on – trends, risk factors and policy implications in global obesity. Nat Rev Endocrinol 2020; 16(11): 615–6. doi: 10.1038/s41574-020-00411-y. PubMed PMID: WOS:000565173100001.
- De Lorenzo A, Romano L, Di Renzo L, Di Lorenzo N, Cenname G, Gualtieri P. Obesity: a preventable, treatable, but relapsing disease. Nutrition 2020; 71: 110615. doi: 10.1016/j.nut.2019.110615. PubMed PMID: 31864969.
- Akhlaghi M. Dietary approaches to stop hypertension (DASH): potential mechanisms of action against risk factors of the metabolic syndrome. Nutr Res Rev 2020; 33(1): 1–18. doi: 10.1017/s0954422419000155. PubMed PMID: WOS:000531843200001.
- Jastreboff AM, Kotz CM, Kahan S, Kelly AS, Heymsfield SB. Obesity as a disease: the obesity society 2018 position statement. Obesity 2019; 27(1): 7–9. doi: 10.1002/oby.22378. PubMed PMID: WOS:000453750700001.
- Malik VS, Willett WC, Hu FB. Global obesity: trends, risk factors and policy implications. Nat Rev Endocrinol 2013; 9(1): 13–27. doi: 10.1038/nrendo.2012.199. PubMed PMID: WOS:000312387900006.
- Sun W, Dong H, Balaz M, Slyper M, Drokhlyansky E, Colleluori G, et al. snRNA-seq reveals a subpopulation of adipocytes that regulates thermogenesis. Nature 2020; 587(7832): 98. doi: 10.1038/s41586-020-2856-x. PubMed PMID: WOS:000582810000003.
- Coelho M, Oliveira T, Fernandes R. Biochemistry of adipose tissue: an endocrine organ. Archiv Med Sci 2013; 9(2): 191–200. doi: 10.5114/aoms.2013.33181. PubMed PMID: WOS:000317994900001.
- Medina-Gomez G. Mitochondria and endocrine function of adipose tissue. Best Pract Res Clin Endocrinol Metab 2012; 26(6): 791–804. doi: 10.1016/j.beem.2012.06.002. PubMed PMID: WOS:000312466500008.
- Inagaki T, Sakai J, Kajimura S. Transcriptional and epigenetic control of brown and beige adipose cell fate and function. Nat Rev Mol Cell Biol 2016; 17(8): 480–95. doi: 10.1038/nrm.2016.62. PubMed PMID: WOS:000380745800008.
- Marlatt KL, Ravussin E. Brown adipose tissue: an update on recent findings. Curr Obes Rep 2017; 6(4): 389–96. doi: 10.1007/s13679-017-0283-6. PubMed PMID: WOS:000417072000005.
- Ikeda K, Maretich P, Kajimura S. The common and distinct features of brown and beige adipocytes. Trends Endocrinol Metab 2018; 29(3): 191–200. doi: 10.1016/j.tem.2018.01.001. PubMed PMID: WOS:000425589200007.
- Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang A-H, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 2012; 150(2): 366–76. doi: 10.1016/j.cell.2012.05.016. PubMed PMID: WOS:000306595700015.
- Alipoor E, Hosseinzadeh-Attar MJ, Rezaei M, Jazayeri S, Chapman M. White adipose tissue browning in critical illness: a review of the evidence, mechanisms and future perspectives. Obes Rev 2020; 21(12): e13085. doi: 10.1111/obr.13085. PubMed PMID: WOS:000544280200001.
- Fernandez-Verdejo R, Marlatt KL, Ravussin E, Galgani JE. Contribution of brown adipose tissue to human energy metabolism. Mol Aspects Med 2019; 68: 82–9. doi: 10.1016/j.mam.2019.07.003. PubMed PMID: WOS:000482103700007.
- Abdullahi A, Jeschke MG. Taming the flames: targeting white adipose tissue browning in hypermetabolic conditions. Endocr Rev 2017; 38(6): 538–49. doi: 10.1210/er.2017-00163. PubMed PMID: WOS:000419059200003.
- Carey AL, Kingwell BA. Brown adipose tissue in humans: therapeutic potential to combat obesity. Pharmacol Ther 2013; 140(1): 26–33. doi: 10.1016/j.pharmthera.2013.05.009. PubMed PMID: WOS:000325123500003.
- Jang KB, Kim SW. Supplemental effects of dietary nucleotides on intestinal health and growth performance of newly weaned pigs. J Anim Sci 2019; 97(12): 4875–82. doi: 10.1093/jas/skz334. PubMed PMID: WOS:000507889900018.
- Hossain MS, Koshio S, Ishikawa M, Yokoyama S, Sony NM. Dietary effects of adenosine monophosphate to enhance growth, digestibility, innate immune responses and stress resistance of juvenile red sea bream, Pagrus major. Fish Shellfish Immunol 2016; 56: 523–33. doi: 10.1016/j.fsi.2016.08.009. PubMed PMID: WOS:000383292200058.
- Martinez-Puig D, Manzanilla EG, Morales J, Borda E, Perez JF, Pineiro C, et al. Dietary nucleotide supplementation reduces occurrence of diarrhoea in early weaned pigs. Livest Sci 2007; 108(1–3): 276–9. doi: 10.1016/j.livsci.2007.01.099. PubMed PMID: WOS:000247123100068.
- Carver JD. Dietary nucleotides: effects on the immune and gastrointestinal systems. Acta Paediatr 1999; 88: 83–8. doi: 10.1080/080352599750029790. PubMed PMID: WOS:000083296700015.
- Lopez-Navarro AT, Ortega MA, Peragon J, Bueno JD, Gil A, Sanchez-Pozo A. Deprivation of dietary nucleotides decreases protein synthesis in the liver and small intestine in rats. Gastroenterology 1996; 110(6): 1760–9. doi: 10.1053/gast.1996.v110.pm8964401. PubMed PMID: BIOSIS:PREV199699059291.
- Duan Y, Li F, Tan B, Lin B, Kong X, Li Y, et al. Myokine interleukin-15 expression profile is different in suckling and weaning piglets. Anim Nutr 2015; 1(1): 30–5. doi: 10.1016/j.aninu.2015.02.005. PubMed PMID: MEDLINE: 29766983.
- Alonso-Andres P, Albasanz JL, Ferrer I, Martin M. Purine-related metabolites and their converting enzymes are altered in frontal, parietal and temporal cortex at early stages of Alzheimer’s disease pathology. Brain Pathol 2018; 28(6): 933–46. doi: 10.1111/bpa.12592. PubMed PMID: WOS:000457460300012.
- Fredholm BB. Adenosine-a physiological or pathophysiological agent? J Mol Med 2014; 92(3): 201–6. doi: 10.1007/s00109-013-1101-6. PubMed PMID: WOS:000334268800002.
- Ming D, Ninomiya Y, Margolskee RF. Blocking taste receptor activation of gustducin inhibits gustatory responses to bitter compounds. Proc Natl Acad Sci U S A 1999; 96(17): 9903–8. doi: 10.1073/pnas.96.17.9903. PubMed PMID: BIOSIS:PREV199900415233.
- Kiyohara S, Hidaka I, Tamura T. The anterior cranial gustatory pathway in fish. Experientia 1975; 31(9): 1051–3. doi: 10.1007/bf02326954. PubMed PMID: MEDLINE: 1175743.
- Liu YL, Zhang YM, Yin J, Ruan Z, Wu X, Yin YL. Uridine dynamic administration affects circadian variations in lipid metabolisms in the liver of high-fat-diet-fed mice. Chronobiol Int 2019; 36(9): 1258–67. doi: 10.1080/07420528.2019.1637347. PubMed PMID: WOS:000476378100001.
- Tie HM, Wu P, Jiang WD, Liu Y, Kuang SY, Zeng YY, et al. Dietary nucleotides supplementation affect the physicochemical properties, amino acid and fatty acid constituents, apoptosis and antioxidant mechanisms in grass carp (Ctenopharyngodon idellus) muscle. Aquaculture 2019; 502: 312–25. doi: 10.1016/j.aquaculture.2018.12.045. PubMed PMID: WOS:000455344800039.
- Hoang Do H. Overview of the application of nucleotide in aquaculture. J Coast Life Med 2016; 4(10): 816–23. doi: 10.12980/jclm.4.2016J6-165. PubMed PMID: BIOSIS:PREV201600799008.
- Masic U, Yeomans MR. Umami flavor enhances appetite but also increases satiety. Am J Clin Nutr 2014; 100(2): 532–8. doi: 10.3945/ajcn.113.080929. PubMed PMID: WOS:000339599100006.
- Tan C, Ji Y, Zhao X, Xin Z, Li J, Huang S, et al. Effects of dietary supplementation of nucleotides from late gestation to lactation on the performance and oxidative stress status of sows and their offspring. Anim Nutr 2021; 7(1): 111–8. doi: 10.1016/j.aninu.2020.10.004
- Tan CQ, Li JY, Ji YC, Yang YY, Zhao XC, Chen MX, et al. Effects of dietary supplementation of different amounts of yeast extract on oxidative stress, milk components, and productive performance of sows. Anim Feed Sci Technol 2021; 274: 114648. doi: 10.1016/j.anifeedsci.2020.114648
- Ardiansyah, Inagawa Y, Koseki T, Agista AZ, Ikeda I, Goto T, et al. Adenosine and adenosine-5 ‘-monophosphate ingestion ameliorates abnormal glucose metabolism in mice fed a high-fat diet. BMC Complement Altern Med 2018; 18: 304. doi: 10.1186/s12906-018-2367-6. PubMed PMID: WOS:000450532100002.
- Fukumori Y, Takeda H, Fujisawa T, Ushijima K, Onodera S, Shiomi N. Blood glucose and insulin concentrations are reduced in humans administered sucrose with inosine or adenosine. J Nutr 2000; 130(8): 1946–9. PubMed PMID: BIOSIS:PREV200000382331.
- Cha SH, Wolfgang M, Tokutake Y, Chohnan S, Lane MD. Differential effects of central fructose and glucose on hypothalamic malonyl-CoA and food intake. Proc Natl Acad Sci U S A 2008; 105(44): 16871–5. doi: 10.1073/pnas.0809255105. PubMed PMID: WOS:000260913800016.
- Pimentel GD, Ropelle ER, Rocha GZ, Carvalheira JBC. The role of neuronal AMPK as a mediator of nutritional regulation of food intake and energy homeostasis. Metabolism 2013; 62(2): 171–8. doi: 10.1016/j.metabol.2012.07.001. PubMed PMID: WOS:000314436300001.
- Salati LM, Gross CJ, Henderson LM, Savaiano DA. Absorption and metabolism of adenine, adenosine-5’-monophosphate, adenosine and hypoxanthine by the isolated vascularly perfused rat small intestine. J Nutr 1984; 114(4): 753–60. PubMed PMID: MEDLINE: 6716178.
- Farmer SR. Transcriptional control of adipocyte formation. Cell Metab 2006; 4(4): 263–73. doi: 10.1016/j.cmet.2006.07.001. PubMed PMID: WOS:000241182900004.
- Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature 2006; 444(7121): 847–53. doi: 10.1038/nature05483. PubMed PMID: WOS:000242805400041.
- Gao J, Xiong R, Xiong D, Zhao W, Zhang S, Yin T, et al. The adenosine monophosphate (AMP) analog, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) inhibits hepatosteatosis and liver tumorigenesis in a high-fat diet murine model treated with diethylnitrosamine (DEN). Med Sci Monit 2018; 24: 8533–43. doi: 10.12659/msm.910544. PubMed PMID: WOS:000451809200002.
- Blondin DP, Labbe SM, Noll C, Kunach M, Phoenix S, Guerin B, et al. Selective impairment of glucose but not fatty acid or oxidative metabolism in brown adipose tissue of subjects with type 2 diabetes. Diabetes 2015; 64(7): 2388–97. doi: 10.2337/db14-1651. PubMed PMID: WOS:000356934000022.
- Fuller-Jackson JP, Henry BA. Adipose and skeletal muscle thermogenesis: studies from large animals. J Endocrinol 2018; 237(3): R99–115. doi: 10.1530/joe-18-0090. PubMed PMID: WOS:000438182500002.
- Townsend KL, An D, Lynes MD, Huang TL, Zhang HB, Goodyear LJ, et al. Increased mitochondrial activity in BMP7-treated brown adipocytes, due to increased CPT1- and CD36-mediated fatty acid uptake. Antioxid Redox Signal 2013; 19(3): 243–57. doi: 10.1089/ars.2012.4536. PubMed PMID: WOS:000321040300004.
- Feldmann HM, Golozoubova V, Cannon B, Nedergaard J. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab 2009; 9(2): 203–9. doi: 10.1016/j.cmet.2008.12.014. PubMed PMID: WOS:000263269400011.
- Ji S, You Y, Kerner J, Hoppel CL, Schoeb TR, Chick WSH, et al. Homozygous carnitine palmitoyltransferase 1b (muscle isoform) deficiency is lethal in the mouse. Mol Genet Metab 2008; 93(3): 314–22. doi: 10.1016/j.ymgme.2007.10.006. PubMed PMID: WOS:000253603300122.
- Barbera MJ, Schluter A, Pedraza N, Iglesias R, Villarroya F, Giralt M. Peroxisome proliferator-activated receptor alpha activates transcription of the brown fat uncoupling protein-1 gene: a link between regulation of the thermogenic and lipid oxidation pathways in the brown fat cell. J Biol Chem 2001; 276(2): 1486–93. doi: 10.1074/jbc.M006246200. PubMed PMID: BIOSIS:PREV200100226156.
- Singh AK, Aryal B, Chaube B, Rotllan N, Varela L, Horvath TL, et al. Brown adipose tissue derived ANGPTL4 controls glucose and lipid metabolism and regulates thermogenesis. Mol Metab 2018; 11: 59–69. doi: 10.1016/j.molmet.2018.03.011. PubMed PMID: WOS:000439548700005.
- Bartelt A, Bruns OT, Reimer R, Hohenberg H, Ittrich H, Peldschus K, et al. Brown adipose tissue activity controls triglyceride clearance. Nat Med 2011; 17(2): 200-U93. doi: 10.1038/nm.2297. PubMed PMID: WOS:000286969900028.
- JohanssonA SM, Lindgren E, Yang J-N, Herling AW, Fredholm BB. Adenosine A(1) receptors regulate lipolysis and lipogenesis in mouse adipose tissue – interactions with insulin. Eur J Pharmacol 2008; 597(1–3): 92–101. doi: 10.1016/j.ejphar.2008.08.022. PubMed PMID: WOS:000260920300015.
- Dhalla AK, Santikul M, Smith M, Wong M-Y, Shryock JC, Belardinelli L. Antilipolytic activity of a novel partial A(1) adenosine receptor agonist devoid of cardiovascular effects: comparison with nicotinic acid. J Pharmacol Exp Ther 2007; 321(1): 327–33. doi: 10.1124/jpet.106.114421. PubMed PMID: WOS:000244989600036.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors retain copyright of their work, with first publication rights granted to SNF Swedish Nutrition Foundation. Read the full Copyright- and Licensing Statement.