Healthy expansion of adipose tissue maintains metabolic homeostasis by storing excess chemical energy in increased fat mass. The STAT5-PPAR gamma pathway reportedly regulates adipocyte differentiation, lipid metabolism and adipogenesis. Ginsenoside Rg3 is one of the diverse groups of steroidal saponins, the major active components of ginseng, which have demonstrated pharmacological properties. In this study, we evaluated the therapeutic effects of ginsenoside Rg3 under pathological conditions in vitro and in vivo. We examined the effects of ginsenoside Rg3 on glucose level, insulin sensitivity and lipogenesis in high-fat diet-fed C57BL/6 mice. Ginsenoside Rg3 was also applied to the pre-adipocyte cell line 3T3-L1 to assess the impact on lipogenesis. Ginsenoside Rg3 reduced epididymal white adipose tissue (eWAT) size and hepatic steatosis, and the amount of triglycerides (TGs) in both eWAT and liver. Similar to the murine model, Rg3-treated 3T3-L1 cells showed a reduction in lipid accumulation and amount of total TGs. Ginsenoside Rg3 regulates the expression of PPAR gamma though STAT5 in vitro and in vivo. According to our results, lipid metabolism-related genes were downregulated in the high-fat mice and 3T3-L1 cell line. Rg3 shows potential for the amelioration of obesity-induced pathology, acting though STAT5-PPAR gamma to facilitate the healthy functioning of adipose tissue. This is the first report of evidence that obesity-induced insulin resistance and lipotoxicity can be treated with ginsenoside Rg3, which acts though the STAT5-PPAR gamma pathway in vivo and in vitro.

The amyloid precursor protein (APP) has been extensively investigated for its role in the production of amyloid beta (Aβ), a plaque-forming peptide in Alzheimer’s disease (AD). Epidemiological evidence suggests type 2 diabetes is a risk factor for AD. The pancreas is an essential regulator of blood glucose levels through the secretion of the hormones insulin and glucagon. Pancreatic dysfunction is a well-characterized consequence of type 1 and type 2 diabetes. In this study, we have examined the expression and processing of pancreatic APP to test the hypothesis that APP may play a role in pancreatic function and the pathophysiology of diabetes. Our data demonstrate the presence of APP within the pancreas, including pancreatic islets in both mouse and human samples. Additionally, we report that the APP/PS1 mouse model of AD overexpresses APP within pancreatic islets, although this did not result in detectable levels of Aβ. We compared whole pancreas and islet culture lysates by Western blot from C57BL/6 (WT), APP^−/− and APP/PS1 mice and observed APP-dependent differences in the total protein levels of GLUT4, IDE and BACE2. Immunohistochemistry for BACE2 detected high levels in pancreatic α cells. Additionally, both mouse and human islets processed APP to release sAPP into cell culture media. Moreover, sAPP stimulated insulin but not glucagon secretion from islet cultures. We conclude that APP and its metabolites are capable of influencing the basic physiology of the pancreas, possibly through the release of sAPP acting in an autocrine or paracrine manner.

The thyroid gland, necessary for normal human growth and development, functions as an essential regulator of metabolism by the production and secretion of appropriate levels of thyroid hormone. However, assessment of abnormal thyroid function may be challenging suggesting a more fundamental understanding of normal function is needed. One way to characterize normal gland function is to study the epigenome and resulting transcriptome within its constituent cells. This study generates the first published reference epigenomes for human thyroid from four individuals using ChIP-seq and RNA-seq. We profiled six histone modifications (H3K4me1, H3K4me3, H3K27ac, H3K36me3, H3K9me3, H3K27me3), identified chromatin states using a hidden Markov model, produced a novel quantitative metric for model selection and established epigenomic maps of 19 chromatin states. We found that epigenetic features characterizing promoters and transcription elongation tend to be more consistent than regions characterizing enhancers or Polycomb-repressed regions and that epigenetically active genes consistent across all epigenomes tend to have higher expression than those not marked as epigenetically active in all epigenomes. We also identified a set of 18 genes epigenetically active and consistently expressed in the thyroid that are likely highly relevant to thyroid function. Altogether, these epigenomes represent a powerful resource to develop a deeper understanding of the underlying molecular biology of thyroid function and provide contextual information of thyroid and human epigenomic data for comparison and integration into future studies.