期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 94, 期 9, 页码 3521-3529出版社
ENDOCRINE SOC
DOI: 10.1210/jc.2009-0212
关键词
-
资金
- National Institutes of Health [DK062948, DK060837, DK70648, M01 RR001032, D36836]
- Diabetes Genome Anatomy Project
- Graetz Family Foundation
- General Clinical Research Center
- Diabetes and Endocrinology Research Center
- Joslin Diabetes Center
- Sigrid Juselius Foundation
- Maud Kuistila Foundation
- Northern Savo Cultural Foundation
- Viipuri Tuberculosis Foundation
Context: Fatty liver is an important complication of obesity; however, regulatory mechanisms mediating altered gene expression patterns have not been identified. Objective: The aim of the study was to identify novel transcriptional changes in human liver that could contribute to hepatic lipid accumulation and associated insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis. Design: We evaluated gene expression in surgical liver biopsies from 13 obese (nine with type 2 diabetes) and five control subjects using Affymetrix U133A microarrays. PCR validation was performed in liver biopsies using an additional 16 subjects. We also tested thyroid hormone responses in mice fed chow or high-fat diet. Setting: Recruitment was performed in an academic medical center. Participants: Individuals undergoing elective surgery for obesity or gallstones participated in the study. Results: The top-ranking gene set, down-regulated in obese subjects, was comprised of genes previously demonstrated to be positively regulated by T-3 in human skeletal muscle (n = 399; P < 0.001; false discovery rate = 0.07). This gene set included genes related to RNA metabolism (SNRPE, HNRPH3, TIA1, and SFRS2), protein catabolism (PSMA1, PSMD12, USP9X, IBE2B, USP16, and PCMT1), and energy metabolism (ATP5C1, COX7C, UQCRB). We verified thyroid hormone regulation of these genes in the liver after injection of C57BL/6J mice with T-3 (100 mu g/100 g body weight); furthermore, T-3-induced increases in expression of these genes were abolished by high-fat diet. In agreement, expression of these genes inversely correlated with liver fat content in humans. Conclusions: These data suggest that impaired thyroid hormone action may contribute to altered patterns of gene expression in fatty liver. (J Clin Endocrinol Metab 94: 3521-3529, 2009)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据