Obesity has become an epidemic, prompting advances in therapies targeting this condition. Estrogen-related receptor α (ESRRA), a transcription factor, plays pivotal roles in energy metabolism across diverse tissues. Studies have demonstrated that loss of Esrra leads to fat malabsorption and resistance to diet-induced obesity. However, the reliance of these studies on germline Esrra mutants overlooks the tissue-specific implications of ESRRA in diet-induced obesity. Notably, Esrra exhibits high expression in the gastrointestinal (GI) tract relative to other tissues. Given the critical role of the GI tract in dietary lipid metabolism, this study employs mouse genetics and genomics approaches to dissect the specific impact of intestinal ESRRA along with investigating its role in diet-induced obesity.