Project description:Microalgal lipid, a feasible substrate for biofuel, is typically accumulated during the stationary growth phase. Generating strains which trigger lipogenesis from the exponential growth phase will enhance lipid productivity, reduce cost of biofuel production. We characterized a lipid-rich microalgal mutant, Dunaliella tertiolecta, which exhibited a six-fold enhancement of neutral lipids production in the exponential growth phase with marginal compromise on growth (4%). Using transcriptomics and metabolomics, regulatory mechanisms of the mutant were uncovered.
Project description:Glucagon supports glucose homeostasis by stimulating hepatic gluconeogenesis, in part by promoting the uptake and conversion of amino acids into gluconeogenic precursors. Genetic disruption or pharmacologic inhibition of glucagon signaling results in elevated plasma amino acids, and compensatory glucagon hypersecretion involving expansion of pancreatic α-cell mass. Regulation of pancreatic α- and β-cell growth has drawn a lot of attention because of potential therapeutic implications. Recent findings indicate that hyperaminoacidemia triggers pancreatic α-cell proliferation via an mTOR-dependent pathway. We confirm and extend these findings by demonstrating that glucagon pathway blockade selectively increases expression of the sodium-coupled neutral amino acid transporter Slc38a5 in a subset of highly proliferative α-cells, and that Slc38a5 is critical for the pancreatic response to glucagon pathway blockade; most notably, mice deficient in Slc38a5 exhibit markedly decreased α-cell hyperplasia to glucagon pathway blockade-induced hyperaminoacidemia. These results show that Slc38a5 is a key component of the feedback circuit between glucagon receptor signaling in the liver and amino acid-dependent regulation of pancreatic α-cell mass in mice.