Investigated bone marrow metabolism in response to acute overnutrition (high calorie diet) and calorie deprivation (fasting). Bone marrow serum and peripheral serum were collected before and after each dietary intervention. Using proteomics analyses of the sera, we characterized nutritional influences on the local and systemic environments. In brief, proteomic analysis of the bone marrow serum after high calorie diet showed an upregulation of proteins related to an inflammatory/complement pathway, while bone marrow serum after fasting showed a significant downregulation of inflammatory/complement pathway proteins. In contrast, the peripheral serum showed signs of an increased inflammatory response that may be due to a rapid increase in body weight and fat mass seen in participants after 10 days of a high calorie diet. After fasting, peripheral serum did show a strong inflammatory response, but there was evidence of increased lipid biosynthesis. Overall, our results demonstrate key differences in inflammatory response and lipid metabolism between high calorie diet and fasting, despite a nearly identical bone marrow adipose phenotype.