Postprandial NMR-Based Metabolic Exchanges Reflect Impaired Phenotypic Flexibility across Splanchnic Organs in the Obese Yucatan Mini-Pig.

Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI Publishing

Magnetic Resonance Spectroscopy*; Animal Nutritional Physiological Phenomena/*physiology ; Intestinal Mucosa/*metabolism ; Liver/*metabolism ; Obesity/*metabolism ; Postprandial Period/*physiology ; Swine, Miniature/*metabolism; Animals ; Blood Glucose/metabolism ; Diet, High-Fat/adverse effects ; Dietary Sucrose/adverse effects ; Energy Metabolism ; Female ; Homeostasis ; Insulin Resistance ; Obesity/etiology ; Swine

The postprandial period represents one of the most challenging phenomena in whole-body metabolism, and it can be used as a unique window to evaluate the phenotypic flexibility of an individual in response to a given meal, which can be done by measuring the resilience of the metabolome. However, this exploration of the metabolism has never been applied to the arteriovenous (AV) exploration of organs metabolism. Here, we applied an AV metabolomics strategy to evaluate the postprandial flexibility across the liver and the intestine of mini-pigs subjected to a high fat-high sucrose (HFHS) diet for 2 months. We identified for the first time a postprandial signature associated to the insulin resistance and obesity outcomes, and we showed that the splanchnic postprandial metabolome was considerably affected by the meal and the obesity condition. Most of the changes induced by obesity were observed in the exchanges across the liver, where the metabolism was reorganized to maintain whole body glucose homeostasis by routing glucose formed de novo from a large variety of substrates into glycogen. Furthermore, metabolites related to lipid handling and energy metabolism showed a blunted postprandial response in the obese animals across organs. Finally, some of our results reflect a loss of flexibility in response to the HFHS meal challenge in unsuspected metabolic pathways that must be further explored as potential new events involved in early obesity and the onset of insulin resistance.

FASEB J. 2015 Nov;29(11):4600-13. (PMID: 26198450)
J Am Coll Cardiol. 2016 Sep 20;68(12):1294-6. (PMID: 27634120)
Cell Cycle. 2014;13(16):2494-500. (PMID: 25486190)
Nat Commun. 2016 Feb 03;7:8994. (PMID: 26839171)
J Proteome Res. 2016 Jun 3;15(6):1862-74. (PMID: 27115730)
Br J Nutr. 2000 Oct;84(4):449-58. (PMID: 11103215)
Am J Physiol. 1969 Apr;216(4):946-52. (PMID: 4887278)
Nat Med. 2011 Apr;17(4):448-53. (PMID: 21423183)
Mol Metab. 2020 Mar;33:23-37. (PMID: 31402327)
J Clin Endocrinol Metab. 2013 Jun;98(6):E1060-5. (PMID: 23633210)
Nature. 2012 Nov 15;491(7424):384-92. (PMID: 23151581)
Cell Metab. 2014 Nov 4;20(5):898-909. (PMID: 25307860)
Sci Rep. 2019 Aug 29;9(1):12527. (PMID: 31467335)
Nat Rev Endocrinol. 2014 Dec;10(12):723-36. (PMID: 25287287)
BMC Gastroenterol. 2015 Sep 16;15:119. (PMID: 26376914)
Clin Nutr. 2019 Dec 17;:. (PMID: 31899037)
Gut. 2012 Apr;61(4):543-53. (PMID: 22110050)
Cell Metab. 2019 Sep 3;30(3):594-606.e3. (PMID: 31257152)
FASEB J. 2018 Oct;32(10):5447-5458. (PMID: 29718708)
J Nutr Biochem. 2019 Mar;65:72-82. (PMID: 30654277)
Nutrients. 2019 Jun 16;11(6):. (PMID: 31208147)
BMC Bioinformatics. 2011 Jun 22;12:253. (PMID: 21693065)
J Comp Physiol B. 2009 Jan;179(1):1-56. (PMID: 18597096)
Nat Rev Mol Cell Biol. 2016 Jul;17(7):451-9. (PMID: 26979502)
Am J Clin Nutr. 1995 Apr;61(4):827-30. (PMID: 7702026)
Nutrients. 2019 Feb 19;11(2):. (PMID: 30791497)
Diabetologia. 2007 Sep;50(9):1867-1879. (PMID: 17618414)
J Anim Sci. 1989 Feb;67(2):386-402. (PMID: 2539347)
Eur J Nutr. 2018 Feb;57(1):119-135. (PMID: 27568059)
Genes Nutr. 2014 Sep;9(5):423. (PMID: 25106484)
Metabolites. 2020 May 07;10(5):. (PMID: 32392884)
Diabetes. 2020 Jun;69(6):1164-1177. (PMID: 32184272)
Nutrition. 2018 Jun;50:66-73. (PMID: 29547796)
PLoS One. 2016 Feb 10;11(2):e0148361. (PMID: 26863521)
Nutrients. 2018 Nov 21;10(11):. (PMID: 30469379)
Diabetes. 1984 Dec;33(12):1188-99. (PMID: 6094292)
BMC Bioinformatics. 2012 Dec 06;13:325. (PMID: 23216942)
PLoS Comput Biol. 2017 Nov 3;13(11):e1005752. (PMID: 29099853)
Metabolomics. 2012 Apr;8(2):347-359. (PMID: 22448156)
Diabetes. 2003 Oct;52(10):2453-60. (PMID: 14514627)
Biochem J. 1985 Sep 15;230(3):675-81. (PMID: 4062872)
Cancer Metab. 2019 Apr 24;7:3. (PMID: 31049200)
Gastroenterology. 2007 Aug;133(2):496-506. (PMID: 17681171)
J Biomed Res. 2017 Nov 01;:. (PMID: 29089472)
Diabetologia. 1999 Aug;42(8):926-31. (PMID: 10491751)
J Anim Sci Biotechnol. 2020 Feb 12;11:5. (PMID: 32082565)
Am J Physiol Regul Integr Comp Physiol. 2007 Apr;292(4):R1400-7. (PMID: 17158265)
Atheroscler Suppl. 2008 Sep;9(2):7-13. (PMID: 18653387)

AlimH Institut National de la Recherche Agronomique

Keywords: arteriovenous differences; energy metabolism; high fat-high sucrose diet; intestine; liver; metabolomics; mini-pigs; phenotypic flexibility; postprandial

0 (Blood Glucose)
0 (Dietary Sucrose)

Date Created: 20200823 Date Completed: 20210402 Latest Revision: 20210402

20250114

PMC7468879

10.3390/nu12082442

32823827