title: Regulation of fatty acid composition and lipid storage by thyroid hormone in mouse liver.
abstract: BACKGROUND
  Thyroid hormones (THs) are potent hormones modulating liver lipid homeostasis. The perturbation of lipid homeostasis is a hallmark of non-alcoholic fatty liver disease (NAFLD), a very common liver disorder. It was reported that NAFLD patients were associated with higher incidence of hypothyroidism. However, whether abnormal thyroid function contributes to the pathogenesis of NAFLD remains unclear.
  
  
  RESULTS
  We used in vivo models to investigate the influence of hypothyroidism and TH on hepatic lipid homeostasis. We did not observe hepatic triglyceride accumulation in the liver of hypothyroid mice, although the liver was enlarged. We then characterized the hepatic fatty acid composition with gas chromatography-mass spectrometry in mice under different thyroid states. We found that hypothyroidism decreased saturated fatty acid (SFA) content while TH treatment restored the level of SFA. In agreement with this finding, we observed that the expression of acetyl-CoA carboxylase 1 and fatty acid synthase, the rate-limit enzymes for de novo lipogenesis (DNL), decreased in hypothyroid mice while increased after TH treatment. We also found that the ratio of C18:1n-9/C18:0 and C16:1n-7/C16:0 was decreased by TH treatment, suggesting the activity of stearoyl-CoA desaturase-1 was suppressed. This finding indicated that TH is able to suppress triglyceride accumulation by reducing fatty acid desaturation. Additionally, we found that hepatic glycogen content was substantially influenced by TH status, which was associated with glycogen synthase expression. The increased glycogen storage might explain the enlarged liver we observed in hypothyroid mice.
  
  
  CONCLUSIONS
  Taken together, our study here suggested that hypothyroidism in mice might not lead to the development of NAFLD although the liver became enlarged. However, disturbed TH levels led to altered hepatic fatty acid composition and glycogen accumulation.
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.|Clinical Research Center of Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Yao
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Sarina
authors.initials: S
authors.lastname: Hou
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.|Clinical Research Center of Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.|Clinical Research Center of Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Xia
authors.affiliation: Clinical Research Center of Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.|Department of Nutrition, Shanghai Xuhui Central Hospital, Shanghai 200031, China.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.|Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China.
authors.forename: Huiyong
authors.initials: H
authors.lastname: Yin
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.|Clinical Research Center of Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.|Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Ying
keywords: Fatty acid; Glycogen; Liver; NAFLD; Thyroid hormone
references.citation: Prog Lipid Res. 2004 Mar;43(2):91-104
references.pmid: 14654089
references.citation: Am J Clin Nutr. 2013 Aug;98(2):319-26
references.pmid: 23803879
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15490-5
references.pmid: 17878314
references.citation: PLoS One. 2012;7(7):e41478
references.pmid: 22911796
references.citation: J Hepatol. 2012 Jan;56(1):248-54
references.pmid: 21827732
references.citation: Endocrinology. 2007 Mar;148(3):1206-17
references.pmid: 17122078
references.citation: Endocrinology. 2013 Jan;154(1):537-49
references.pmid: 23221600
references.citation: Hepatology. 2012 Jun;55(6):2005-23
references.pmid: 22488764
references.citation: Am J Clin Nutr. 2011 Aug;94(2):431-8
references.pmid: 21697077
references.citation: Mol Endocrinol. 2002 Jun;16(6):1257-68
references.pmid: 12040013
references.citation: Endocrinology. 2010 Dec;151(12):5952-60
references.pmid: 20881246
references.citation: Endocr Rev. 1993 Jun;14(3):348-99
references.pmid: 8319599
references.citation: Endocrinology. 2009 Jun;150(6):2940-7
references.pmid: 19282388
references.citation: Hepatology. 2009 Feb;49(2):407-17
references.pmid: 19072834
references.citation: Nat Rev Drug Discov. 2009 Apr;8(4):308-20
references.pmid: 19337272
references.citation: J Biol Chem. 2009 Feb 27;284(9):5637-44
references.pmid: 19119140
references.citation: Endocrinology. 2005 Mar;146(3):1568-75
references.pmid: 15591136
references.citation: Prog Lipid Res. 2009 Jan;48(1):1-26
references.pmid: 18824034
references.citation: Hepatology. 2007 Oct;46(4):1081-90
references.pmid: 17654743
references.citation: Mol Endocrinol. 2000 Jul;14(7):947-55
references.pmid: 10894146
references.citation: Free Radic Biol Med. 2014 May;70:223-32
references.pmid: 24607715
references.citation: Ann Intern Med. 1998 Jul 15;129(2):144-58
references.pmid: 9669977
references.citation: Am J Physiol Gastrointest Liver Physiol. 2006 May;290(5):G852-8
references.pmid: 16603729
references.citation: Biochem Biophys Res Commun. 1997 Apr 28;233(3):838-43
references.pmid: 9168944
references.citation: Nutr Res Pract. 2013 Aug;7(4):294-301
references.pmid: 23964317
references.citation: J Clin Invest. 2003 Aug;112(4):497-9
references.pmid: 12925689
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6409-14
references.pmid: 15096593
references.citation: FASEB J. 2008 Aug;22(8):2981-9
references.pmid: 18434432
references.citation: Early Hum Dev. 2001 Nov;65 Suppl:S31-41
references.pmid: 11755033
references.citation: J Clin Invest. 2012 Jul;122(7):2428-38
references.pmid: 22684107
references.citation: Physiol Rev. 2001 Jul;81(3):1097-142
references.pmid: 11427693
references.citation: J Clin Gastroenterol. 2003 Oct;37(4):340-3
references.pmid: 14506393
references.citation: JAMA. 2004 Jan 14;291(2):228-38
references.pmid: 14722150
references.citation: Best Pract Res Clin Gastroenterol. 2013 Aug;27(4):553-63
references.pmid: 24090942
references.citation: J Biol Chem. 2003 Mar 7;278(10):7964-72
references.pmid: 12493735
references.citation: Eur J Clin Nutr. 1999 Apr;53 Suppl 1:S53-65
references.pmid: 10365981
references.citation: Exp Physiol. 2009 Oct;94(10):1079-87
references.pmid: 19542188
references.citation: Mol Endocrinol. 2009 Mar;23(3):308-15
references.pmid: 19131509
references.citation: Diabetes Metab. 2003 Nov;29(5):478-85
references.pmid: 14631324
references.citation: J Hepatol. 2012 Jul;57(1):150-6
references.pmid: 22425701