Biology subjects

Wang, B. Z.

Publications and source records attributed to Wang, B. Z..

3 recordsLinked to original sources

bioRxiv2023

Gender-specific impact of trans 10, cis 12-conjugated linoleic acid on pai transgenic female mice

Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones.

physiology↗

bioRxiv2023

Metabolic impact of trans 10, cis 12-conjugated linoleic acid in pai transgenic mice

Trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) from ruminant-derived foodstuffs can induce body fat loss in mammals after oral administration, while its mechanism on fat reduction has yet to be clarified fully until now. In the current study, a transgenic mouse that produced t10c12-CLA had been generated by inserting the Propionibacterium acnes isomerase (Pai) expression cassette into the Rosa26 locus, and its male offspring were used to decipher an irreversible long-term impact of t10c12-CLA on health and its mechanism of action. Compared to their wild-type C57BL/6J littermates, comprehensive phenotype profiling of biallelic pai/pai mice indicated that white fat was decreased while brown fat was increased reversely; meanwhile, more heat was released and the central activities were reduced. Besides decreased plasma triglycerides in both pai genotypes and increased serum FGF21 in pai/wt mice, RNA and protein analysis revealed that the fatty acid oxidation and thermogenesis capacity of brown adipose tissues were elevated via CPT1B and UCP1/2 over-expression. The results indicate that the t10c12-CLA-induced fat loss might be caused by the excess FGF21 and the increased mass and extra thermogenesis of brown adipose tissue in transgenic mice.

physiology↗

bioRxiv2022

STK25 inhibits PKA signaling by phosphorylating PRKAR1A

In the heart, Protein Kinase A (PKA) is critical for activating calcium handling and sarcomeric proteins in response to beta adrenergic stimulation leading to increased myocardial contractility and performance. The catalytic activity of PKA is tightly regulated by regulatory subunits which inhibit the catalytic subunit until released by cAMP binding. Phosphorylation of Type II regulatory subunits promotes PKA activation, however the role of phosphorylation in Type I regulatory subunits remain uncertain. Here we utilized human induced pluripotent stem cell cardiomyocytes (iPSC-CM) to identify STK25 as a kinase of the Type Ia regulatory subunit PRKAR1A. Phosphorylation of PRKAR1A led to inhibition of PKA kinase activity and increased binding to the catalytic subunit in the presence of cAMP. Stk25 knockout in mice diminished Prkar1a phosphorylation, increased Pka activity and augmented contractile response to beta adrenergic stimulation. Together, these data support STK25 as a negative regulator of PKA signaling through phosphorylation of PRKAR1A.

physiology↗