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Biomedical subjects

Jaesung Park

Publications and source records attributed to Jaesung Park.

3 recordsLinked to original sources

Linking visceral fat accumulation to gut microbiota: key bacterial taxa and their roles in the glycogen synthesis pathway.

Obesity, marked by visceral fat accumulation, has a complex relationship with the gut microbiome that impacts body weight and fat accumulation. However, previous studies did not account for fat distribution, reflecting only overall fat mass, leaving specifics of this relationship partially understood. Here we analyzed the mechanistic links between visceral fat and the microbiome in a large cohort of healthy Koreans. Using permutational multivariate analysis of variance and prediction modeling, we examined associations between microbial profiles and metabolic variables including insulin, triglycerides, waist circumference and visceral fat. The strongest correlations were noted with specific enterotypes. Shotgun sequencing revealed that visceral fat is linked to the glycogen synthesis pathway influenced by Dorea longicatena and Bifidobacterium adolescentis. This suggests that these specific microbial signatures and their associated functional potential play a role in visceral fat-related obesity. To validate these findings, we conducted an in vivo study using diet-induced obesity mouse model. Oral administration of D. longicatena or B. adolescentis significantly promoted body weight gain and fat mass expansion and induced hepatic lipogenic gene upregulation. The prevalence of these strains in Korean and American populations highlights their global relevance, contributing to the development of personalized treatments and advanced health strategies.

Journal Article↗

Oxygen uptake rates and liver-specific functions of hepatocyte and 3T3 fibroblast co-cultures.

Bioartificial liver (BAL) devices have been developed to treat patients undergoing acute liver failure. One of the most important parameters to consider in designing these devices is the oxygen consumption rate of the seeded hepatocytes which are known to have oxygen consumption rates 10 times higher than most other cell types. Hepatocytes in various culture configurations have been tested in BAL devices including those formats that involve co-culture of hepatocytes with other cell types. In this study, we investigated, for the first time, oxygen uptake rates (OUR)s of hepatocytes co-cultured with 3T3-J2 fibroblasts at various hepatocyte to fibroblast seeding ratios. OURs were determined by measuring the rate of oxygen disappearance using a ruthenium-coated optical probe after closing and sealing the culture dish. Albumin and urea production rates were measured to assess hepatocyte function. Lower hepatocyte density co-cultures demonstrated significantly higher OURs (2 to 3.5-fold) and liver- specific functions (1.6-fold for albumin and 4.5-fold for urea production) on a per cell basis than those seeded at higher densities. Increases in OUR correlated well with increased liver-specific functions. OURs (V(m)) were modeled by fitting Michaelis-Menten kinetics and the model predictions closely correlated with the experimental data. This study provides useful information for predicting BAL design parameters that will avoid oxygen limitations, as well as maximize metabolic functions.

3T3 Cells↗

Microfabricated grooved substrates as platforms for bioartificial liver reactors.

An extracorporeal bioartificial liver device has the potential to provide temporary hepatic support for patients with liver failure. Our goal was to optimize the flow environment for the cultured hepatocytes in a flat-plate bioreactor, specifically focusing on oxygen delivery using high medium flow rates while reducing the detrimental effects of the resulting shear stresses. We used photolithographic techniques to fabricate microgrooves onto the underlying glass substrate. The microgrooves, perpendicular to the axial flow direction, protected the hepatocytes from the shear stress induced by the flowing medium. Using finite element analysis, we found that the velocity gradient change near the cell surface (i.e., bottom of the grooves) was smaller than that near the top surface of the flow channel, indicating that the grooves would provide protection to the attached cells from the mechanical effects of the flowing medium. We also determined that the shear stress at the cell surface could be reduced by as much as 30 times (channel height of 100 microm) in the grooved-substrate (0.5 dyn/cm(2)) bioreactor compared to the flat-substrate (15 dyn/cm(2)) bioreactor for a medium flow rate of 4.0 mL/min. Albumin and urea synthesis rates of hepatocytes cocultured with 3T3-J2 fibroblasts remained stable over 5 days of perfusion in the grooved-substrate bioreactor, whereas in the flat-substrate bioreactor they decreased over the same time period. These studies indicate that under "high" flow conditions the microgrooved-substrate in the bioreactor can decrease the detrimental effects of shear stress on the hepatocytes while providing adequate oxygenation, thereby resulting in stable liver-specific function.

3T3 Cells↗