Function and regulation of Letmd1 in metabolic signaling

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Modified Project Summary/Abstract Section This short-term award is to support the collection of preliminary data for submission of a conventional research grant that focuses on the role of Letmd1 in metabolic regulation. Thermogenic brown adipose tissue (BAT) has been associated with cardiometabolic health in humans. It is important to understand how BAT thermogenesis is controlled because enhancing BAT thermogenesis could lead to new therapeutic interventions with tangible health benefits. We recently demonstrated that Letmd1 is selectively enriched in BAT and that global Letmd1 knockout (KO) mice exhibit severe impairment of cold-induced thermogenesis. In Aim 1, we will perform respirometry with global KO mouse tissues to determine the effect on OXPHOS respiration. In Aim 2, we will determine if the expression of Letmd1 is altered in a mouse bariatric surgery model. In Aim 3, we will test if changes in Letmd1 protein phosphorylation can be detected. In Aim 4, we will generate a fat-specific Letmd1 KO mouse model. These Aims will establish feasibility for the conventional research grant application to be submitted.