The age-related differences in obese and fatty acid synthase gene expression in white adipose tissue of rat

To determine the effects of age and lipoic acid supplementation on hepatic gene expression, we fed young (3 mo) and old (24 mo) male Fischer 344 rats a diet with or without 0.2% (wt/wt) R-α-lipoic acid (LA) for 2 wk. Total RNA isolated from liver tissue was analyzed by Affymetrix microarray to examine changes in transcriptional profiles. Results showed elevated proinflammatory gene expression in the aging liver and evidence for increased immune cell activation and tissue remodeling, together representing 45% of the age-related transcriptome changes. In addition, age-related increases in transcripts of genes related to fatty acid, triglyceride, and cholesterol synthesis, including acetyl-CoA carboxylase-β (Acacb) and fatty acid synthase (Fasn), were observed. Supplementation of old animals with LA did not reverse the necroinflammatory phenotype but, intriguingly, altered the expression of genes governing circadian rhythm. Most notably, Arntl, Npas2, and Per changed in a coordinated manner with respect to rhythmic transcription. LA further caused a decrease in transcripts of several bile acid and lipid synthesis genes, including Acacb and Fasn, which are regulated by first-order clock transcription factors. Similar effects of LA supplementation on bile acid and lipid synthesis genes were observed in young animals. Transcript changes of lipid metabolism genes were corroborated by a decrease in FASN and ACC protein levels. We conclude that advanced age is associated with a necroinflammatory phenotype and increased lipid synthesis, while chronic LA supplementation influences hepatic genes associated with lipid and energy metabolism and circadian rhythm, regardless of age.

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Cold-induced lipid dynamics and transcriptional programs in white adipose tissue

BMC Biology ◽

10.1186/s12915-019-0693-x ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 9

Author(s):

Ziye Xu ◽

Wenjing You ◽

Yanbing Zhou ◽

Wentao Chen ◽

Yizhen Wang ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Fatty Acid ◽

White Adipose Tissue ◽

Cold Exposure ◽

Fatty Acid Elongation ◽

Rna Seq ◽

Short Term ◽

Lipid Dynamics ◽

Expression Of Genes

Abstract Background In mammals, cold exposure induces browning of white adipose tissue (WAT) and alters WAT gene expression and lipid metabolism to boost adaptive thermogenesis and maintain body temperature. Understanding the lipidomic and transcriptomic profiles of WAT upon cold exposure provides insights into the adaptive changes associated with this process. Results Here, we applied mass spectrometry and RNA sequencing (RNA-seq) to provide a comprehensive resource for describing the lipidomic or transcriptome profiles in cold-induced inguinal WAT (iWAT). We showed that short-term (3-day) cold exposure induces browning of iWAT, increases energy expenditure, and results in loss of body weight and fat mass. Lipidomic analysis shows that short-term cold exposure leads to dramatic changes of the overall composition of lipid classes WAT. Notably, cold exposure induces significant changes in the acyl-chain composition of triacylglycerols (TAGs), as well as the levels of glycerophospholipids and sphingolipids in iWAT. RNA-seq and qPCR analysis suggests that short-term cold exposure alters the expression of genes and pathways involved in fatty acid elongation, and the synthesis of TAGs, sphingolipids, and glycerophospholipids. Furthermore, the cold-induced lipid dynamics and gene expression pathways in iWAT are contrary to those previously observed in metabolic syndrome, neurodegenerative disorders, and aging, suggesting beneficial effects of cold-induced WAT browning on health and lifespan. Conclusion We described the significant alterations in the composition of glyphospholipids, glycerolipids, and sphingolipids and expression of genes involved in thermogenesis, fatty acid elongation, and fatty acid metabolism during the response of iWAT to short-term cold exposure. We also found that some changes in the levels of specific lipid species happening after cold treatment of iWAT are negatively correlated to metabolic diseases, including obesity and T2D.

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