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. 2014 Jul 30:4:38.
doi: 10.1186/2045-3701-4-38. eCollection 2014.

Regulation of fatty acid composition and lipid storage by thyroid hormone in mouse liver

Xuan Yao #  1   2 , Sarina Hou #  1 , Duo Zhang  1   2 , Hongfeng Xia  1   2 , Yu-Cheng Wang  2   3 , Jingjing Jiang  4 , Huiyong Yin  1   5 , Hao Ying  1   2   5
Affiliations

Regulation of fatty acid composition and lipid storage by thyroid hormone in mouse liver

Xuan Yao et al. Cell Biosci. .

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.

Keywords: Fatty acid; Glycogen; Liver; NAFLD; Thyroid hormone.

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Figures

Figure 1
Figure 1
Liver weight and hepatic lipid content. (A) Liver weight to body weight ratio of control group (Ctrl), hypothyroid group (Hypo) and T3-treated group (T3) mice. n = 6 in each group. (B) Hepatic triglyceride content in Ctrl, Hypo and T3 mice. n = 6 ~ 8 in each group. (C) Oil red O staining and H&E staining of Ctrl, Hypo and T3 mice. Scale bar indicates a length of 200μm. *P < 0.05 vs. Ctrl, ‡P < 0.05 vs. Hypo.
Figure 2
Figure 2
Hepatic ACC1 and FASN expression levels. Western blotting analysis of ACC1 and FASN in liver from control group (Ctrl), hypothyroid group (Hypo) and T3-treated group (T3).
Figure 3
Figure 3
Unsaturated fatty acid (UFA) concentration and SCD-1 expression. (A) C16:1n-7/C16:0 and C18:1n-9/C18:0 ratios were compared and used as surrogate measures of hepatic SCD-1 activity. n = 5 in each group (B) RT-PCR analysis of SCD-1 gene expression in mouse liver from control group (Ctrl), hypothyroid group (Hypo) and T3-treated group (T3). 18s amplified in parallel served as internal reference. n = 6 in each group. (C) Western blotting analysis of SCD-1 with β-Actin as an indication of equal protein loading. (D) Fatty acids were grouped according to the degree of saturation and the amount of fatty acid belonging to the same group was added up. The relative contents of each group were compared across the Ctrl, Hypo and T3. n = 5 in each group. (E) The ratios between n-6 PUFA and n-3 PUFA in different groups were compared. n = 5 in each group. *P < 0.05 vs. Ctrl, ‡P < 0.05 vs. Hypo.
Figure 4
Figure 4
Hepatic glycogen content and the expression of gene related to glycogen synthesis. (A) Hepatic glycogen content was measured from liver samples obtained in group control group (Ctrl), hypothyroid group (Hypo) and T3-treated group (T3). n = 6 in each group. (B) PAS staining of liver section from Ctrl, Hypo and T3 indicated the presence of glycogen. (C) RT-PCR analysis of GYS2 gene expression in mouse liver from Ctrl, Hypo and T3. 18s amplified in parallel served as internal reference. n = 6 ~ 8 in each group. (D) Western blotting analysis of GYS2 with α-Tubulin as an indication of equal protein loading. *P < 0.05 vs. Ctrl, ‡P < 0.05 vs. Hypo.
Figure 5
Figure 5
Flow charts illustrating the preferred metabolic pathways under hypothyroid status before and after T3 treatment. The hypothyroidism was compared with Control (A) while hypothyroidism + T3 status was compared with hypothyroidism (B).
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References

    1. Baxter JD, Webb P. Thyroid hormone mimetics: potential applications in atherosclerosis, obesity and type 2 diabetes. Nat Rev Drug Discov. 2009;8:308–320. doi: 10.1038/nrd2830. - DOI - PubMed
    1. Lazar MA. Thyroid hormone action: a binding contract. J Clin Invest. 2003;112:497–499. doi: 10.1172/JCI19479. - DOI - PMC - PubMed
    1. Helfand M, Redfern CC. Clinical guideline, part 2. Screening for thyroid disease: an update. American College of Physicians. Ann Intern Med. 1998;129:144–158. doi: 10.7326/0003-4819-129-2-199807150-00020. - DOI - PubMed
    1. Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, Franklyn JA, Hershman JM, Burman KD, Denke MA, Gorman C, Cooper RS, Weissman NJ, Gorman C, Cooper RS, Weissman NJ. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004;291:228–238. doi: 10.1001/jama.291.2.228. - DOI - PubMed
    1. Refetoff S, Weiss RE, Usala SJ. The syndromes of resistance to thyroid hormone. Endocr Rev. 1993;14:348–399. - PubMed