Villalobos et al. have explored the role of ATP-binding cassette family C member 1 (ABCC1) and its capability to modulate glucocorticoid actions. Using Abcc1 knockout mice, they showed raised corticosterone levels in skeletal muscle and adipose tissue and enhanced insulin resistance in knockout animals fed a high-fat diet, when compared with wild type controls.

Proteomic and RNA sequencing analyses revealed that knocking out Abcc1 enhances the transcriptional response to an obesogenic diet in adipose tissue but not in skeletal muscle. Key pathways related to glucose metabolism, particularly OXPHOS machinery and Glut4, are disrupted in both tissues. The findings indicate ABCC1’s role in glucose homeostasis, demonstrating diet-dependent effects not linked to altered tissue glucocorticoid concentrations. This research suggests that ABCC1 is crucial for metabolic responses to dietary fat intake, potentially impacting obesity and type 2 diabetes.

Future studies should investigate the mechanisms by which ABCC1 deficiency amplifies transcriptional responses to a high-fat diet and disrupts glucose metabolism, offering insights into potential therapeutic targets for metabolic diseases.

Read the full article in Journal of Endocrinology 262 e240024

https://doi.org/10.1530/JOE-24-0024