Epigenetic suppression of creatine kinase B in adipocytes links endoplasmic reticulum stress to obesity-associated inflammation.

In white adipose tissue, disturbed creatine metabolism through reduced creatine kinase B (CKB) transcription contributes to obesity-related inflammation. However, the mechanisms regulating CKB expression in human white adipocytes remain unclear. By screening conditions perturbed in obesity, we identified endoplasmic reticulum (ER) stress as a key suppressor of CKB transcription across multiple cell types.

Reduced adipocyte glutaminase activity promotes energy expenditure and metabolic health.

Glutamine and glutamate are interconverted by several enzymes and alterations in this metabolic cycle are linked to cardiometabolic traits. Herein, we show that obesity-associated insulin resistance is characterized by decreased plasma and white adipose tissue glutamine-to-glutamate ratios. We couple these stoichiometric changes to perturbed fat cell glutaminase and glutamine synthase messenger RNA and protein abundance, which together promote glutaminolysis.

Extracellular matrix hyaluronan modulates fat cell differentiation and primary cilia dynamics.

Hyaluronan is an important extracellular matrix component, with poorly documented physiological role in the context of lipid-rich adipose tissue. We have investigated the global impact of hyaluronan removal from adipose tissue environment by in vitro exposure to exogenous hyaluronidase (or heat inactivated enzyme). Gene set expression analysis from RNA sequencing revealed downregulated adipogenesis as a main response to hyaluronan removal from human adipose tissue samples, which was confirmed by hyaluronidase-mediated inhibition of adipocyte differentiation in the 3T3L1 adipose cell line.