GSE38144
Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism.
The effects of adiponectin on hepatic glucose and lipid metabolism at transcriptional level are largely unknown. We profiled hepatic gene expression in adiponectin knockout (KO) and wild-type (WT) mice by RNA-Seq. Comparing to WT mice, adiponectin KO mice exhibited decreased mRNA expression of rate-limiting enzymes in several important glucose and lipid metabolic pathways including glycolysis, TCA cycle, fatty-acid activation and synthesis, triglyceride synthesis and cholesterol synthesis. In addition, binding of the transcription factor Hnf4a to DNAs encoding several key metabolic enzymes was reduced in KO mice, suggesting that adiponectin might regulate hepatic gene expression via Hnf4a.  Phenotypically, adiponectin KO mice possessed smaller epididymal fat pads and showed reduced body weights comparing to WT mice. When fed a high fat diet, adiponectin KO mice showed significantly reduced lipid accumulation in the livers. These lipogenic defects are consistent with the downregulation of lipogenic genes in the KO mice. Overall design: Mice were fasted overnight before euthanization. Liver tissues from WT or adiponectin KO male mice (n = 9-10) at 12 weeks of age were harvested and subjected to total RNA extraction using an RNeasy Plus Mini Kit (Qiagen, Valencia, CA).  Total RNA from nine to ten mice of the same strain was pooled together as one biological sample. The mRNA sequencing samples were prepared using the Illumina sample preparation protocol (RS-930-1001, Illumina, Inc. San Diego, CA). The cDNA fragments of 200–250 bp were purified on an agarose gel and then enriched by PCR with Phusion polymerase. The cDNA libraries were sequenced by an Illumina Genome analyzer II at the Whitehead Genome Technology Core.