Provided are methods of treating a liver disease in a subject, comprising administering to the subject: i) an inhibitor of patatin like phospholipase domain containing 3 (PNPLA3) expression; and ii) an agonist of glucagon receptor and/or glucagon-like peptide-1 (GLP-1) receptor. Also provided pharmaceutical and kits comprising i) an inhibitor of PNPLA3 expression; and ii) an agonist of glucagon receptor and/or GLP-1 receptor.

Recombinant DNA techniques are used to produce oleaginous recombinant cells that produce triglyceride oils having desired fatty acid profiles and regiospecific or stereospecific profiles. Genes manipulated include those encoding stearoyl-ACP desturase, delta 12 fatty acid desaturase, acyl-ACP thioesterase, ketoacyl-ACP synthase, and lysophosphatidic acid acyltransferase. The oil produced can have enhanced oxidative or thermal stability, or can be useful as a frying oil, shortening, roll-in shortening, tempering fat, cocoa butter replacement, as a lubricant, or as a feedstock for various chemical processes. The fatty acid profile can be enriched in midchain profiles or the oil can be enriched in triglycerides of the saturated-unsaturated-saturated type.

The invention provides a Saccharomyces cerevisiae strain for producing a human milk lipid substitute. By integrating a heterologous lysophosphatidic acid acyltransferase into Saccharomyces cerevisiae and knocking out its own natural lysophosphatidic acid acyltransferase, the content of palmitic acid (C16:0) at Sn-2 position of triacylglycerol produced by Saccharomyces cerevisiae is increased, to synthesize a human milk lipid substitute. On this basis, a metabolic pathway related gene is knocked out, to further increase the content of human milk lipid substitute in the product. In the present invention, a human milk lipid substitute is de novo synthesized by Saccharomyces cerevisiae for the first time, in which the total fatty acid is 15% or more, and the relative content of C16:0 at Sn-2 position reaches about 60%.

Provided herein are triglyceride oil compositions enriched in 1,3-dioleoyl-2-palmitoylglycerol (OPO). Further provided herein are methods of producing non-naturally occurring triglyceride oil compositions enriched in OPO from non-naturally occurring microorganisms and applications thereof in a variety of end products, including, for example, polyols and nutritional supplements.

This disclosure describes transgenic plants engineered for enhanced amounts of fatty acids and triacylglycerols (TAGs) in vegetative tissues. This document describes novel approaches to develop biomass crops, such as Sorghum, for production of vegetative sources of vegetable oils in leaves and stems as alternative renewable diesel and sustainable aviation fuel (SAF) feedstocks. A new approach is described for engineering high vegetative oil production that involves expression of variant medium-chain fatty acid acyl-acyl carrier protein (AGP) thioesterases to drive vegetable oil production. This approach has been shown to be effective with two different acyl-ACP thioesterases, and the high oil production is maintained over multiple genetic generations in greenhouse and field cultivation systems.