Transcriptomic changes upon ESRRA loss in the small intestinal epithelium

Amidst the obesity epidemic and advancements in satiety-targeting therapies, the transcriptional control of energy metabolism is crucial for managing obesity. The transcription factor Estrogen-related receptor α (ESRRA) regulates genes involved in mitochondrial biogenesis, gluconeogenesis, oxidative phosphorylation, and fatty acid metabolism. Although not essential for basic cellular function, ESRRA is vital for energy supply during physiological and pathological challenges. Studies show Esrra mutant mice have impaired fat metabolism and absorption, with germline Esrra loss conferring resistance to high-fat diet (HFD)-induced obesity. However, these studies often overlook tissue-specific roles. Esrra knockdown in the medial pre-frontal cortex reduces feeding and HFD-induced obesity, indicating possible neurological involvement. Notably, ESRRA is highly expressed in the gastrointestinal (GI) tract, a key player in dietary lipid metabolism and target of weight loss therapies.This study aims to investigate the impact of intestinal ESRRA and determine whether it contributes to resistance to diet-induced obesity.