CIDEA blocking peptide

In this study, we examined gene expression in order to identify genes that are differentially expressed between the hepatocytes of Sichuan White geese and Landes geese. We hypothesized that such genes may be involved in the different predispositions between these two species to develop hepatic steatosis. RNA was isolated from primary hepatocytes of the two species, and suppression subtractive hybridization was employed to screen for genes that showed differences in mRNA expression. We built and characterized two reciprocal cDNA libraries that were enriched in genes up-regulated in Landes geese or Sichuan White geese. Using dot blot analysis we identified 128 of 600 randomly selected sequences that demonstrated differential expression between the two species. Of these differentially expressed genes, 115 sequences shared high homology with 46 known genes and 13 sequences corresponded to eight novel expressed sequence tags (ESTs). Based on functional clustering, up and down-regulated genes were mostly related to lipid metabolism, nuclear mRNA splicing, enzyme activity and transcription control. The expression of 18 selected clones was further studied by quantitative PCR. The data showed that eight clones similar to the genes ACSL5, CTGF, CIDEA, PPAR gamma, PCK, GSTS1, RPS4X, and THBS1 had significantly higher expression levels in the hepatocytes of Landes geese. In contrast, seven clones similar to the genes ADH5, YBX1, ASAH1, UCB, AOPVLDL, SCD-1, and ELOVL-6 had significantly higher expression levels in the hepatocytes of Sichuan White geese.

Various endocrine factors contribute to cold-induced white adipose tissue (WAT) browning, but glucagon has largely been ignored. The purpose of the current investigation was to determine if glucagon was required for the effects of cold on WAT browning. Utilizing whole-body glucagon receptor knockout (Gcgr(-/-)) mice and their wild-type (WT) littermate controls, we examined the response of inguinal WAT (iWAT) and interscapular brown adipose tissue (BAT) to an acute (48 h) cold stress or challenge with the beta 3-adrenergic agonist CL316,243. The effects of glucagon alone on the induction of thermogenic genes in adipose tissue from C57BL6/J mice were also examined. Gcgr(-/-) mice displayed modest increases in indices of browning at room temperature while displaying a blunted induction of Ucp1, Cidea, and Ffg21 mRNA expression in iWAT following cold exposure. Similarly, cold induced increases in mitochondrial DNA copy number, and the protein content of mitochondrial respiratory chain complexes, UCP1, and PGC1 were attenuated in iWAT from Gcgr(-/-) mice. In BAT, the induction of thermogenic markers following cold exposure was reduced, but the effect was less pronounced than in iWAT. Glucagon treatment increased the expression of thermogenic genes in both iWAT and BAT of C57BL6/J mice. In response to CL316,243, circulating fatty acids, glycerol, and the phosphorylation of hormone-sensitive lipase were attenuated in iWAT of Gcgr(-/-) mice. We provide evidence that glucagon is sufficient for the induction of thermogenic genes in iWAT, and the absence of intact glucagon signaling blunts the cold-induced browning of WAT, possibly due, in part, to impaired adrenergic signaling.