In this paper, we demonstrated that male mice housed under thermoneutral conditions exhibit significant weight gain, hyperglycemia, hyperlipidemia, increased marrow adiposity, and secondary osteoporosis in response to HFD feeding, and that the daily administration of the pan-IP6K inhibitor TNP affords protection against HFD-induced metabolic derangements, resulting in a significant preservation of bone volume, density, and microarchitecture. This evidence concerns the gene PPIP5K1 and Hyperglycemia.