Sucnr1, also known as GPR91, belongs to the family of G protein-coupled receptors (GPCR). It is activated by succinate, a citric acid cycle intermediate. The succinate/Sucnr1 axis is involved in indicating local stress that may impact cellular metabolism, and has potential as an innovative drug target [1].

Adipocyte-specific deletion of Sucnr1 influences leptin response to feeding, highlighting its role in energy metabolism via modulating the circadian clock and leptin expression [2]. Myeloid-specific deficiency in Sucnr1 promotes a local pro-inflammatory phenotype and disrupts glucose homeostasis in mice, suggesting its importance in macrophage-mediated anti-inflammatory responses and metabolic regulation [3]. In β cells, mice with β cell-specific Sucnr1 deficiency exhibit impaired glucose tolerance and insulin secretion on a high-fat diet, showing Sucnr1's essentiality for insulin secretion in diet-induced insulin resistance [5]. Sucnr1 deficiency in mice fed a choline-deficient high-fat diet provokes both beneficial and detrimental effects in the liver, disrupting glucose homeostasis [4]. Also, succinate-induced renal injury in mice was found to be mediated via Sucnr1 activation, causing tubular epithelial cell apoptosis [6].

In conclusion, Sucnr1 plays crucial roles in multiple biological processes such as energy metabolism, immune response, insulin secretion, and organ-specific functions. Gene knockout mouse models have been instrumental in revealing its role in diseases like obesity-related metabolic disorders, non-alcoholic fatty liver disease, and renal injury, providing valuable insights into potential therapeutic targets for these conditions.