Succinate receptor 1 signaling mutually depends on subcellular localization and cellular metabolism.

Succinate is a pivotal tricarboxylic acid cycle metabolite but also specifically activates the G- and G-coupled succinate receptor 1 (SUCNR1). Contradictory roles of succinate and succinate-SUCNR1 signaling include reports about its anti- or pro-inflammatory effects. The link between cellular metabolism and localization-dependent SUCNR1 signaling qualifies as a potential cause for the reported conflicts.

An E115A Missense Variant in CERS2 Is Associated With Increased Sleeping Energy Expenditure and Hepatic Insulin Resistance in American Indians.

Genetic determinants of interindividual differences in energy expenditure (EE) are largely unknown. Sphingolipids, such as ceramides, have been implicated in the regulation of human EE via mitochondrial uncoupling. In this study, we investigated whether genetic variants within enzymes involved in sphingolipid synthesis and degradation affect EE and insulin-related traits in a cohort of American Indians informative for 24-h EE and glucose disposal rates during a hyperinsulinemic-euglycemic clamp.

Combining metabolic phenotype determination with metabolomics and transcriptional analyses to reveal pathways regulated by hydroxycarboxylic acid receptor 2.

Background: The adaptation of cellular metabolism is considered a hallmark of cancer. Oncogenic signaling pathways support tumorigenesis and cancer progression through the induction of certain metabolic phenotypes associated with altered regulation of key metabolic enzymes. Hydroxycarboxylic acid receptor 2 (HCA) is a G protein-coupled receptor previously shown to act as a tumor suppressor.

Hydroxycarboxylic acid receptor 3 and GPR84 - Two metabolite-sensing G protein-coupled receptors with opposing functions in innate immune cells.

G protein-coupled receptors (GPCRs) are key regulatory proteins of immune cell function inducing signaling in response to extracellular (pathogenic) stimuli. Although unrelated, hydroxycarboxylic acid receptor 3 (HCA) and GPR84 share signaling via Gα proteins and the agonist 3-hydroxydecanoic acid (3HDec). Both receptors are abundantly expressed in monocytes, macrophages and neutrophils but have opposing functions in these innate immune cells.

Succinate receptor 1 inhibits mitochondrial respiration in cancer cells addicted to glutamine.

Cancer cells display metabolic alterations to meet the bioenergetic demands for their high proliferation rates. Succinate is a central metabolite of the tricarboxylic acid (TCA) cycle, but was also shown to act as an oncometabolite and to specifically activate the succinate receptor 1 (SUCNR1), which is expressed in several types of cancer. However, functional studies focusing on the connection between SUCNR1 and cancer cell metabolism are still lacking.

Natural biased signaling of hydroxycarboxylic acid receptor 3 and G protein-coupled receptor 84.

Background: Medium-chain fatty acids and their 3-hydroxy derivatives are metabolites endogenously produced in humans, food-derived or originating from bacteria. They activate G protein-coupled receptors, including GPR84 and HCA, which regulate metabolism and immune functions. Although both receptors are coupled to G proteins, share at least one agonist and show overlapping tissue expression, GPR84 exerts pro-inflammatory effects whereas HCA is involved in anti-inflammatory responses.