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Cited by 94Lipid metabolism and biosynthesisAlcohol Consumption and Health EffectsLiver Disease Diagnosis and Treatment

Chronic Alcohol Exposure Disturbs Lipid Homeostasis at the Adipose Tissue-Liver Axis in Mice: Analysis of Triacylglycerols Using High-Resolution Mass Spectrometry in Combination with In Vivo Metabolite Deuterium Labeling

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Wei, Xiaoli, Shi, Xue, Zhong, Wei, Zhao, Yantao, Tang, Yunan, Sun, Wenlong, Yin, Xinmin, Bogdanov, Bogdan +4 more·2013·PLoS ONE
DOI 10.1371/journal.pone.0055382PMC PMC3566154
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Abstract

A method of employing high-resolution mass spectrometry in combination with in vivo metabolite deuterium labeling was developed in this study to investigate the effects of alcohol exposure on lipid homeostasis at the white adipose tissue (WAT)-liver axis in a mouse model of alcoholic fatty liver. In order to differentiate the liver lipids synthesized from the fatty acids that were transported back from adipose tissue and the lipids synthesized from other sources of fatty acids, a two-stage mouse feeding experiment was performed to incorporate deuterium into metabolites. Hepatic lipids extracted from mouse liver, epididymal white adipose tissue (eWAT) and subcutaneous white adipose tissue (sWAT) were analyzed. It was found that 13 and 10 triacylglycerols (TGs) incorporated with a certain number of deuterium were significantly increased in alcohol induced fatty liver at two and four weeks of alcohol feeding periods, respectively. The concentration changes of these TGs ranged from 1.7 to 6.3-fold increase. A total of 14 deuterated TGs were significantly decreased in both eWAT and sWAT at the two and four weeks and the fold-change ranged from 0.19 to 0.77. The increase of deuterium incorporated TGs in alcohol-induced fatty liver and their decrease in both eWAT and sWAT indicate that alcohol exposure induces hepatic influx of fatty acids which are released from WATs. The results of time course analysis further indicate a mechanistic link between adipose fat loss and hepatic fat gain in alcoholic fatty liver.

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  • Acetaldehyde promotes lipolysis in adipose tissue and elevates the amount of free FAs that are absorbed by the liver.

    “Acetaldehyde, in particular, promotes lipolysis in adipose tissue and elevates the amount of free FAs (FFAs) that are absorbed by the liver [15,47].”

    From Pathophysiological Aspects of Alcohol Metabolism in the Liver (2021) · cites this paper as [47]

    The Introduction and Discussion (Temporal Analysis; pages unavailable) link alcohol exposure in mice to adipose lipolysis, fatty-acid release, and transport of those fatty acids to the liver. They do not identify acetaldehyde in particular as the cause, so the claim's specific attribution to acetaldehyde is unsupported. (LLM, conf=0.88)

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Research works printed but not linked: 34

  1. [1]Xiao C, Hsieh J, Adeli K, Lewis GF (2011) Gut-liver interaction in triglyceride-rich lipoprotein metabolism. Am J Physiol Endocrinol Metab 301: E429– 446. 21693689
  2. [2]Sethi JK, Vidal-Puig AJ (2007) Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res 48: 1253– 1262. 17374880 PMC4303760
  3. [3]Cusi K (2010) The role of adipose tissue and lipotoxicity in the pathogenesis of type 2 diabetes. Curr Diab Rep 10: 306– 315. 20556549
  4. [4]Bradbury MW, Berk PD (2004) Lipid metabolism in hepatic steatosis. Clin Liver Dis 8: 639–671, xi. 15331068
  5. [5]Sozio MS, Liangpunsakul S, Crabb D (2010) The role of lipid metabolism in the pathogenesis of alcoholic and nonalcoholic hepatic steatosis. Semin Liver Dis 30: 378– 390. 20960377
  6. [6]Berk PD, Zhou S, Bradbury MW (2005) Increased hepatocellular uptake of long chain fatty acids occurs by different mechanisms in fatty livers due to obesity or excess ethanol use, contributing to development of steatohepatitis in both settings. Trans Am Clin Climatol Assoc 116: 335–344; discussion 345. PMC1473156 16555625
  7. [7]Addolorato G, Capristo E, Greco AV, Stefanini GF, Gasbarrini G (1997) Energy expenditure, substrate oxidation, and body composition in subjects with chronic alcoholism: new findings from metabolic assessment. Alcohol Clin Exp Res 21: 962– 967. 9309302
  8. [8]Addolorato G, Capristo E, Greco AV, Stefanini GF, Gasbarrini G (1998) Influence of chronic alcohol abuse on body weight and energy metabolism: is excess ethanol consumption a risk factor for obesity or malnutrition? J Intern Med 244: 387– 395. 9845854
  9. [9]Kang L, Chen X, Sebastian BM, Pratt BT, Bederman IR, et al (2007) Chronic ethanol and triglyceride turnover in white adipose tissue in rats: inhibition of the anti-lipolytic action of insulin after chronic ethanol contributes to increased triglyceride degradation. J Biol Chem 282: 28465– 28473. 17686776
  10. [10]Zhou SL, Gordon RE, Bradbury M, Stump D, Kiang CL, et al (1998) Ethanol up-regulates fatty acid uptake and plasma membrane expression and export of mitochondrial aspartate aminotransferase in HepG2 cells. Hepatology 27: 1064– 1074. 9537447
  11. [11]Kang X, Zhong W, Liu J, Song Z, McClain CJ, et al (2009) Zinc supplementation reverses alcohol-induced steatosis in mice through reactivating hepatocyte nuclear factor-4alpha and peroxisome proliferator-activated receptor-alpha. Hepatology 50: 1241– 1250. 19637192 PMC2757527
  12. [12]Zhong W, Zhao Y, Tang Y, Wei X, Shi X, et al (2012) Chronic alcohol exposure stimulates adipose tissue lipolysis in mice: role of reverse triglyceride transport in the pathogenesis of alcoholic steatosis. Am J Pathol 180: 998– 1007. 22234172 PMC3349880
  13. [13]Sun X, Tang Y, Tan X, Li Q, Zhong W, et al (2012) Activation of peroxisome proliferator-activated receptor-gamma by rosiglitazone improves lipid homeostasis at the adipose tissue-liver axis in ethanol-fed mice. Am J Physiol Gastrointest Liver Physiol 302: G548– 557. 22173916 PMC3311430
  14. [14]Pouteau E, Beysen C, Saad N, Turner S (2009) Dynamics of adipose tissue development by 2H2O labeling. In Methods Mol Biol 579: 337– 58. 19763484
  15. [15]Wei X, Sun W, Shi X, Koo I, Wang B, et al (2011) MetSign: a computational platform for high-resolution mass spectrometry-based metabolomics. Anal Chem 83: 7668– 7675. 21932828 PMC3196362
  16. [16]Astrand M (2003) Contrast normalization of oligonucleotide arrays. J Comput Biol 10: 95– 102. 12676053
  17. [17]Bolstad BM, Irizarry RA, Astrand M, Speed TP (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19: 185– 193. 12538238
  18. [18]Newton MA, Noueiry A, Sarkar D, Ahlquist P (2004) Detecting differential gene expression with a semiparametric hierarchical mixture method. Biostatistics 5: 155– 176. 15054023
  19. [19]Fisher RA (1948) Questions and answers #14. The American Statistician 2(5): 30– 31.
  20. [21]Sumner LW, Amberg A, Barrett D0, Beale MH, Beger R, et al (2007) Proposed minimum reporting standards for chemical analysis. Metabolomics 3: 211– 221. 24039616 PMC3772505
  21. [22]Wang MY, Grayburn P, Chen S, Ravazzola M, Orci L, et al (2008) Adipogenic capacity and the susceptibility to type 2 diabetes and metabolic syndrome. Proc Natl Acad Sci USA. 105: 6139– 6144. PMC2329698 18413598
  22. [23]Large V, Peroni O, Letexier D, Ray H, Beylot M (2004) Metabolism of lipids in human white adipocyte. Diabetes Metab 30: 294– 309. 15525872
  23. [24]Kang L, Nagy LE (2006) Chronic ethanol feeding suppresses beta-adrenergic receptor-stimulated lipolysis in adipocytes isolated from epididymal fat. Endocrinology 147: 4330– 4338. 16794014 PMC1764504
  24. [25]You M, Rogers CQ (2009) Adiponectin: a key adipokine in alcoholic fatty liver. Exp Biol Med (Maywood) 234: 850– 859. 19491377
  25. [26]Greco AV, Mingrone G, Favuzzi A, Capristo E, Gniuli D, et al (2000) Serum leptin levels in post-hepatitis liver cirrhosis. J Hepatol 33: 38– 42. 10905584
  26. [27]Santolaria F, Pérez-Cejas A, Alemán MR, González-Reimers E, Milena A, et al (2003) Low serum leptin levels and malnutrition in chronic alcohol misusers hospitalized by somatic complications. Alcohol Alcohol 38: 60– 66. 12554610
  27. [28]You M, Considine RV, Leone TC, Kelly DP, Crabb DW (2005) Role of adiponectin in the protective action of dietary saturated fat against alcoholic fatty liver in mice. Hepatology 42: 568– 577. 16108051 PMC1398076
  28. [29]Shen Z, Liang X, Rogers CQ, Rideout D, You M (2010) Involvement of adiponectin-SIRT1-AMPK signaling in the protective action of rosiglitazone against alcoholic fatty liver in mice. Am J Physiol Gastrointest Liver Physiol. 298: G364– 374. PMC2838513 20007851
  29. [30]Tan X, Sun X, Li Q, Zhao Y, Zhong W, et al (2012) Leptin deficiency contributes to the pathogenesis of alcoholic fatty liver disease in mice. Am J Pathol 181: 1279– 1286. 22841822 PMC3463622
  30. [31]Gao B, Bataller R (2011) Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology 141: 1572– 1585. 21920463 PMC3214974
  31. [32]Janero DR, Siuta-Mangano P, Miller KW, Lane MD. Synthesis, processing, and secretion of hepatic very low density lipoprotein. J Cell Biochem. 24(2): 131– 52. 6373801
  32. [33]Yao Z, Zhou H, Figeys D, Wang Y, Sundaram M (2012) Microsome-associated lumenal lipid droplets in the regulation of lipoprotein secretion. Curr Opin Lipidol [Epub ahead of print]. 23123764
  33. [34]Kharbanda KK, Todero SL, Ward BW, Cannella JJ, Tuma DJ (2009) Betaine administration corrects ethanol-induced defective VLDL secretion. Mol Cell Biochem 327: 75– 78. 19219625
  34. [35]Tomita K, Azuma T, Kitamura N, Nishida J, Tamiya G, et al (1999) Hepatocyte growth factor leads to recovery from alcohol-induced fatty liver in rats. J Clin Invest 103: 313– 320. 9927491 PMC407897

Cited by

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Authors
Wei, X., Shi, X., Zhong, W., Zhao, Y., Tang, Y., Sun, W., Yin, X., Bogdanov, B., Kim, S., McClain, C., Zhou, Z., & Zhang, X.
Affiliations
  • University of Louisville (US)
  • University of North Carolina at Greensboro (US)
Corresponding author
  • Zhou, Zhanxiang
  • Zhang, Xiang
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-02-06
Volume
8
Issue
2
Pages
e55382
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0055382
PMC
PMC3566154
OpenAlex
W2139236741
Cited by
94
References
0
Citations by year
2026: 4 · 2025: 6 · 2024: 10 · 2023: 7 · 2022: 9 · 2021: 13 · 2020: 5 · 2019: 8 · 2018: 5 · 2017: 11 · 2016: 6 · 2015: 5 · 2014: 3 · 2013: 2
FWCI
2.49
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • NC Digital Online Collection of Knowledge and Scholarship (The University of North Carolina at Greensboro) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • University of Louisville
  • National Institutes of Health
  • National Institute on Alcohol Abuse and Alcoholism (R01AA018016, R37AA010762, R01AA018844, U01AA021901, P30AA019360, R01AA015970, P01AA017103, R01AA018869, RC2AA019385)
  • National Institute of General Medical Sciences (R01GM087735)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK7071765)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
Keywords
chronic ethanol exposure, alcoholic fatty liver, lipid homeostasis, triglycerides, deuterium labeling, fatty acid uptake, hepatic lipid synthesis, white adipose tissue, hepatic steatosis
MeSH terms
Ethanol, Animals, Deuterium, Fatty Acids, Fatty Liver, Alcoholic, Feeding Methods, Homeostasis, Liver, Male, Mice, Inbred C57BL, Mass Spectrometry, Triglycerides, Subcutaneous Fat, Lipid Metabolism, Mice, Adipose Tissue, White

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