Effect of rosiglitazone on the differential expression of obesity and insulin resistance associated proteins in lep/lep mice

Abstract

Peroxisome proliferator-activated receptors (PPARs) participate in the molecular mechanism of pathologies with altered lipid homeostasis such as type 2 diabetes or obesity. The insulin sensitizer drug, rosiglitazone, has been shown to bind and activate PPAR-gamma1 in adipocytes and PPAR-gamma2 in hepatocytes. The identification of new molecular targets associated with fatty acid oxidation and PPAR-gamma nuclear receptor regulation in insulin resistance tissues is a key research goal. In the present study, we have used a proteomic approach to identify such targets. Lean and obese C57 Bl/6J lep/lep mice were given BRL49653, rosiglitazone, 10 mg/kg diet, by dietary admixture for 7 days. Rosiglitazone normalized the impaired glucose tolerance and dyslipidemia in lep/lep mice but had no significant effect in the lean mice. Samples of liver, white and brown adipose tissue, and muscle proteins were obtained and 100 microg of proteins was arrayed by two-dimensional gel electrophoresis. Thirty-four polypeptides were differentially expressed (p < 0.05) between lep/lep and lean mice and eleven were significantly (p < 0.05) modulated by rosiglitazone treatment of the obese mice. None of the proteins was modulated by rosiglitazone treatment of the lean mice. The identity of these differentially expressed proteins was made using tandem mass spectrometric analysis and revealed components of fatty acid and carbohydrate metabolism as well as proteins with unknown function.

Identification of novel molecular candidates for fatty liver in the hyperlipidemic mouse model, HcB19

“…At present, only a limited number of studies addressing protein expression in hepatic steatosis or NASH have been published (9)(10)(11). The present data identified several proteins that have been implicated in steatosis or NASH in the literature: ATP5B, ALB, FTCD, HPCL2, CAT, HSPA5, and CPS1.…”

“…Proteins induced in these mechanisms may be of great importance in advancing understanding of these processes, or even be potential therapeutic targets. To our knowledge, only a few studies addressed protein expression in NASH (9)(10)(11).…”

Proteomic Analysis of Primary Cultures of Human Adipose-derived Stem Cells

“…Further studies examining the secretosome and subcellular fractions of the human ADAS adipocytes are warranted. Proteomic analyses of murine white adipose tissue have identified up to 27 individual protein features that are modified by high fat diet, insulin treatment, or leptin deficiency (62)(63)(64). The ADAS cell proteome included a high percentage of identical or similar proteins (20 -86%).…”

Proteomics in diabetes research

“…PPAR-γ agonists are known to act via activating a nuclear receptor, thus leading to increased insulin sensitivity. To identify new potential drug targets, the effect of rosiglitazone on different tissues was determined in C57BL/6J lep/lep mice (Sanchez, et al 2003). Initially 34 proteins were shown to be differently expressed between C57BL/6J lep/lep mice and lean littermates.…”