HFD-fed mice developed obesity, hyperglycemia, hyperlipidemia, and secondary osteoporosis, while TNP administration protected mice against HFD-induced metabolic and lipid derangements and preserved bone mass, mineral density, and trabecular microarchitecture, which correlated with reduced serum leptin levels, reduced marrow adiposity, and preservation of marrow resident skeletal stem/progenitor cells (SSPCs). The gene discussed is LEP; the disease is osteoporosis.