Adipocyte-specific tribbles pseudokinase 1 regulates plasma adiponectin and plasma lipids in mice.

Objective: Multiple genome-wide association studies (GWAS) have identified SNPs in the 8q24 locus near TRIB1 that are significantly associated with plasma lipids and other markers of cardiometabolic health, and prior studies have revealed the roles of hepatic and myeloid Trib1 in plasma lipid regulation and atherosclerosis. The same 8q24 SNPs are additionally associated with plasma adiponectin levels in humans, implicating TRIB1 in adipocyte biology. Here, we hypothesize that TRIB1 in adipose tissue regulates plasma adiponectin, lipids, and metabolic health.

Genetics-driven discovery of novel regulators of lipid metabolism.

Purpose Of Review: Residual cardiovascular disease risk and increasing metabolic syndrome risk underscores a need for novel therapeutics targeting lipid metabolism in humans. Unbiased human genetic screens have proven powerful in identifying novel genomic loci, and this review discusses recent developments in such discovery.

Recent Findings: Recent human genome-wide association studies have been completed in incredibly large, detailed cohorts, allowing for the identification of more than 300 genomic loci that participate in the regulation of plasma lipid metabolism.

Regulation of mitochondrial morphology by lipids.

Although great progress has been made in identifying key protein factors that regulate mitochondrial morphology through mediating fission and fusion, signaling lipids are increasingly being recognized as important in the process as well. We review here roles that have been proposed for the signaling and bulk lipids cardiolipin, phosphatidic acid, lysophosphatidic acid, diacylglycerol, and phosphatidylethanolamine and the enzymes that generate or catabolize them in the regulation of mitochondrial morphology in yeast and mammals. Mutations in some of these enzymes are causal in a number of disease settings, highlighting the significance of controlling the lipid environment in this setting.