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Polyphenols have been shown to possess outstanding anti-obesity properties. In this study, the effect of blue honeysuckle berry extract (BHBE) with high polyphenol content on lipid accumulation in adipocytes and the underlying mechanism were investigated for the first time. Composition analysis demonstrated that flavonoids (mainly flavonols and anthocyanins) were the primary polyphenols in BHBE, which contributed to its biological functions. The results of Oil Red O staining combined with triglyceride (TG) content determination showed that BHBE exhibited an obvious inhibitory effect on intracellular lipid accumulation in a dose-dependent manner. BHBE also reduced the protein level of fatty acid synthase (FAS) and increased the phosphorylation level of acetyl-CoA carboxylase (ACC), indicating that lipogenesis was suppressed by BHBE treatment. Moreover, BHBE was found to significantly promote the phosphorylation of AMP-activated protein kinase (AMPK) and further reduce the expression of key transcription factors (PPARγ, C/EBPα, and SREBP-1c) that regulate lipogenesis. In addition, the expression of beige adipocyte markers (Tmem26 and Cd137) and uncoupling protein 1 (UCP1) was increased in BHBE-treated adipocytes. In summary, we consider that BHBE inhibits lipid accumulation in adipocytes by suppressing lipogenesis as well as by promoting beiging of adipocytes. These results support blue honeysuckle berry as a candidate functional food against obesity.

Diabetic nephropathy (DN) affects around 40% of diabetic patients worldwide and has become a major health concern due to its high morbidity and mortality. The progression of DN is characterized by the thickening of glomerular basement membrane, albuminuria and the development of glomerulosclerosis. Renal function is eventually compromised. Due to various hemodynamic and metabolic changes, especially the elevated blood glucose level in diabetic patients, glomerular mesangial cells have been shown to upregulate transforming growth factor-β1 (TGF-β1) level and signaling, resulting in the excessive production of extracellular matrix (ECM) proteins. The atypical expression of the 78-kDa glucose-regulated protein (GRP78) on the cell surface may be associated with this pro-fibrotic effect through its interaction with the TGF-β1 activation process. However, there is no current literature demonstrating the role of cell surface GRP78 (csGRP78) in the pathogenesis of diabetic renal diseases. The purpose of my MSc project was to determine the role of csGRP78 in TGF-β1 synthesis and activation and thereby in the progression of DN. We hypothesized that the increased expression of csGRP78 in response to high glucose exposure stimulates TGF-β1 upregulation through intracellular signaling, as well as its activation through interaction with the latent complex, which leads to the expansion of mesangial matrix. Thesis Master of Science (MSc) Diabetic kidney disease affects around 40% of diabetic patients worldwide and is a major health concern. A major feature of the disease is glomerulosclerosis, which is the scarring of glomeruli. The glomeruli filter blood passing through blood vessels in the kidneys to remove waste, which will then be excreted into urine. In diabetic patients, high blood glucose causes the fibrosis of glomeruli and damages the filtration barrier. As a result, a large amount of proteins leak from the blood into the urine. It has been discovered that TGF-β1 is one of the key molecules mediating the generation of scar tissue in the glomerulus. It promotes the growth of mesangial cells, a major type of kidney glomerular cells, and stimulates their production of extracellular matrix proteins. Our results showed that GRP78, a protein that is primarily expressed in the endoplasmic reticulum and assists with protein folding, moves from the inside of cells to the surface in response to a high glucose environment. Here, we found that it facilitated TGF-β1 signaling. Based on our studies, we propose that when GRP78 is at the cell surface, it enables the release of latent TGF-β1, increasing TGF-β1 activity and thus promoting the development of disease.