Uncovering mechanisms of thiazolidinediones on osteogenesis and adipogenesis using spatial fluxomics.

Objective: Insulin-sensitizing drugs, despite their broad use against type 2 diabetes, can adversely affect bone health, and the mechanisms underlying these side effects remain largely unclear. Here, we investigated the different metabolic effects of a series of thiazolidinediones, including rosiglitazone, pioglitazone, and the second-generation compound MSDC-0602K, on human mesenchymal stem cells (MSCs).

Methods: We developed C subcellular metabolomic tracer analysis measuring separate mitochondrial and cytosolic metabolite pools, lipidomic network-based isotopologue models, and bioorthogonal click chemistry, to demonstrate that MSDC-0602K differentially affected bone marrow-derived MSCs (BM-MSCs) and adipose tissue-derived MSCs (AT-MSCs).

Tissue-specific sex-dependent difference in the metabolism of fatty acid esters of hydroxy fatty acids.

Fatty acid esters of hydroxy fatty acids (FAHFAs) are endogenous bioactive lipids known for their anti-inflammatory and anti-diabetic properties. Despite their therapeutic potential, little is known about the sex-specific variations in FAHFA metabolism. This study investigated the role of sex and Androgen Dependent TFPI Regulating Protein (ADTRP), a FAHFA hydrolase.

Tissue-specific sex difference in the metabolism of fatty acid esters of hydroxy fatty acids.

Fatty acid esters of hydroxy fatty acids (FAHFAs) are endogenous bioactive lipids known for their anti-inflammatory and anti-diabetic properties. Despite their therapeutic potential, little is known about the sex-specific variations in FAHFA metabolism. This study investigated the role of Androgen Dependent TFPI Regulating Protein (ADTRP), a FAHFA hydrolase.