Obesity is a key factor leading to the development of insulin resistance, and its prevalence is increasing all over the world. The general benefits of exercise, both mentally and physically, are widely known, but in recent years, organs such as the intestine, its microbiota, and their crosstalk with other organs have exhibited high research interest. As genetic components affect the response to exercise, twin studies offer unique possibilities to minimize the confounding effects of genetics. This thesis aimed to study the effects of long-term exercise training on liver and intestinal insulin-stimulated glucose uptake (GU), pancreatic and liver fat content, and intestinal microbiota composition. Tissue-specific GU was measured using positron emission tomography (PET), and fat content using magnetic resonance imaging and magnetic resonance spectroscopy, and microbiota composition was studied with 16s rRNA at baseline and after six months of regular exercise training in monozygotic twins discordant for BMI. To gain complementary data on liver GU and inflammation, a supplemental rat study with PET imaging and histological liver sample assessments was done. At baseline, heavier twins had higher liver and pancreatic fat content, disrupted liver metabolism, and worse liver inflammatory state compared to leaner twins. Heavier twins also had lower intestinal GU, while no differences were seen in intestinal microbiota composition between the twin groups. Exercise tended to decrease liver fat in the heavier twins and decreased blood gamma-glutamyl transferase level, an oxidative stress marker. In rats, exercise decreased liver fat content, especially when combined with a dietary switch from a high-fat diet to chow, and reduced liver inflammation. Training increased colonic GU in leaner twins and caused significant changes in intestinal microbiota composition. No change was seen in pancreatic fat content. In conclusion, exercise and exercise combined with dietary change from a high-fat diet to chow caused several improvements in the liver and intestine. The magnitude of the effects driven by exercise varies based on baseline obesity level, as leaner individuals seem to benefit most in colon GU and microbiota composition, while heavier individuals show a reduction in liver fat content and liver inflammation.