Background: Despite the fact that sexual differences increase diabetic risk and contribute to the need for gender-specific care, there remain contradictory results as to whether or not sexual dimorphism increases susceptibility to the development of type 1 diabetes mellitus. Methods: To examine gender-dimorphic regulation of skeletal muscle proteins between healthy control and STZ-induced diabetic rats of both genders, we performed differential proteome analysis using two-dimensional electrophoresis combined with mass spectrometry. Results: Animal experiments revealed that STZ treatment rendered female rats more susceptible to induction of diabetes than their male littermates with significantly lower plasma insulin levels due to hormonal regulation. Proteomic analysis of skeletal muscle identified a total of 21 proteins showing gender-dimorphic differential expression patterns between healthy controls and diabetic rats. Most interestingly, gender-specific proteome comparison showed that male and female rats displayed differential regulation of proteins involved in muscle contraction, carbohydrate, and lipid metabolism, as well as oxidative phosphorylation and cellular stress. Conclusion: The current proteomic study revealed that impaired protein regulation was more prominent in the muscle tissue of female diabetic rats, which were more susceptible to STZ-induced diabetes. We expect that the present proteomic data can provide valuable information for evidence-based gender-specific treatment of diabetes.

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In the present study, we examined differentially regulated plasma proteins between healthy control and streptozotocin (STZ)-induced male and female diabetic rats by 2DE-based proteomic analysis. Animal experiments revealed that significantly lower plasma insulin levels were observed in female diabetic rats, consequently resulting in higher blood glucose levels in female diabetic rats. Importantly, plasma levels of sex hormones were significantly altered in a gender-dependent manner before and after STZ treatment. Results of the animal experiment indicated the existence of sexual dimorphism in the regulation of plasma proteins between healthy control and diabetic rats. Plasma proteome analysis enabled us to identify a total of 38 proteins showing sexual dimorphic regulation patterns. In addition, for the first time, we identified several differentially regulated plasma proteins between healthy control and diabetic rats, including apolipoprotein E, fetuin B, α-1-acid glycoprotein, β-2-glycoprotein 1, 3-hydroxyanthranilate 3,4-dioxygenase, and serum amyloid P-component. To the best of our knowledge, this is the first proteomic approach to address sexual dimorphism in diabetic animals. These proteomic data on gender-dimorphic regulation of plasma proteins provide valuable information that can be used for evidence-based gender-specific clinical treatment of diabetes.

In the present study, we investigated the effects of multi-herbal water extract mixture, Taeumjowi-tang (TH) on liver proteome alteration in mice using twodimensional electrophoresis combined with MALDI-TOF-MS. Animals were fed high-fat diet with or without TH (0.3% wt/wt) supplement for 12 weeks. At the end of 5 th week of experimental diet, mice fed high-fat diet only were subdivided into 2 groups, obesity-prone (OP) and obesityresistant (OR) mice based on weight gain. OR mice gained less body weight compared to OP mice despite of same food intake. TH significantly suppressed weight gain, and proteomic analysis enabled the identification of 49 liver proteins showing differential regulation between OP and OR/TH mice. Combined results of proteomic and western blot analyses revealed decreased lipogenesis via three fatty acid metabolic targets (AMPK, ACC, and FAS) in livers of OR and TH mice. Using bioinformatic classification and network analysis, most of the identified proteins were classified as hydrolases, oxidoreductases, transferases, defense/immunity proteins, and enzyme modulators based on functional analysis of the PANTHER classification system. Combined results of proteomic and bioinformatic analyses using GeneMANIA identified two proteins (LACTB2 and NIT2) in the liver that potentially interact with fatty acid metabolic proteins. Furthermore, these proteins were included in acetylation, phosphoprotein, and metabolic processes in DAVID classification. These proteins were highly expressed in OP mice; however both their transcription and protein expression were lowered by TH treatment. In conclusion, combined data from proteomic and network analyses suggest that TH exerts anti-obesity effects by modulating fatty acid metabolic proteins/genes, particularly via the AMPK pathway. Most targeted proteins/ genes were modulated toward enhancing lipid metabolism in response to TH treatment.

Despite the fact that gender dimorphism in diet-induced oxidative stress is associated with steroid sex hormones, there are some contradictory results concerning roles of steroid hormones in gender dimorphism. To evaluate the role of gender dimorphism as well as the effects of sex steroid hormones in response to high-fat diet (HFD)-induced oxidative stress, we measured cellular levels of major antioxidant proteins in the liver, abdominal white adipose tissue, and skeletal muscles of Sprague-Dawley rats following HFD or sex hormone treatment using Western blot analysis. Animal experiments revealed that 17β-estradiol, (E2) and dihydrotestosterone (DHT) negatively and positively affected body weight gain, respectively. Interestingly, plasma levels of malondialdehyde (MDA) increased in both E2- and DHT-treated rats. We also observed that cellular levels of classical antioxidant proteins, including catalase, glutathion peroxidase, peroxiredoxin, superoxide dismutase, and thioredoxin, were differentially regulated hormone- and gender-dependent manner in various metabolic tissues. In addition, tissue-specific expression of DJ-1 protein with respect to HFD-induced oxidative stress in association with sex steroid hormone treatment was observed for the first time. Taken together, our data show that females were more capable at overcoming oxidative stress than males through feasible expression of antioxidant proteins in metabolic tissues. Although the exact regulatory mechanism of sex hormones in diet-induced oxidative stress could not be fully elucidated, the current data will provide clues regarding the tissue-specific roles of antioxidant proteins during HFD-induced oxidative stress in association with sex steroid hormones.