There continues to be a strong relationship between increased apoA-I and HDL in animal models and reduced atherosclerosis. However, the true potential of mimetic peptides as a means to harness the positive properties of apoA-I remain uncertain. Further, there is some question as to the most appropriate model of insulin resistance and atherosclerosis and it is likely studies in multiple models are needed to identify the true potential of mimetics. Results presented in the current paper do not support a protective role for apoA-I mimetic L4F at a dose of 100 mg/day/ mouse in weight gain, inflammation, insulin resistance, or atherosclerosis in a model of DIO. Future research needs to verify the mechanism of protection and identify an appropriate dosage, route of delivery and timing to effect change on atherosclerosis progression in appropriate models of human disease. The ability for HDL to prevent insulin resistance remains an intriguing idea, and despite results in the current model it warrants further research. Prohibitin 1, a prohibitin family protein, forms a large complex with PHB2 at the inner mitochondrial membrane. PHB1 has emerged as a key regulator of several cellular events, including mitochondrial morphogenesis, cell adhesion, cell cycle regulation, and fat metabolism. For example, PHB1 regulates transcription in the nucleus by interacting with E2F, retinoblastoma protein, and chromatin-remodeling complexes. Repression of E2F-mediated transcription by PHB1 requires histone deacetylation and co-repressors . PHB1 also inhibits DNA replication by interacting with members of Minichromosome maintenance complex of proteins proteins in the nucleus. On the other hand, Perifosine phosphorylation of PHB1 results in its association with the plasma membrane, activation of the Ras–Raf signaling pathway, which regulates epithelial cell adhesion and migration, and metastasis. In light of these findings, PHB1 is a promising target for clinical applications because natural anticancer compounds such as rocaglamide can inhibit the Ras2Raf signaling pathway by binding to PHB1. Among the many emerging roles of PHB1, its role in the maintenance of mitochondrial integrity is perhaps the most important. At the mitochondrial inner membrane, PHB1 and PHB2 assemble into a large ring-like complex that stabilizes newly synthesized mitochondrial respiratory enzymes. Prohibitins also function in cell proliferation and apoptosis by regulating the processing of the dynamin-like GTPase OPA1, thus control morphogenesis of mitochondrial cristae. PHB1-mediated regulation of mitochondrial metabolism also links with cell senescence. For example, Marta et al. have reported that prohibitins promote longevity in Caenorhabditis elegans by affecting mitochondrial function and fat metabolism, which extends life span in certain genetic background. The loss of prohibitin also impairs mitochondrial architecture and results in neurodegeneration in the mouse, which is indicative of aging. PHB1 has many tissue-specific functions. It is strongly expressed by cells such as adipocytes, muscle cells, and b-cells that rely on efficient mitochondrial function and high energy levels. The loss of PHB markedly reduces fat content in adult nematodes and induces mitochondrial damages in b-cells of mammals, which results in the development of diabetes. In addition, PHB1 is critical for adipocyte differentiation, attenuating insulin-stimulated fatty acid and glucose oxidation in adipose tissue. Thus, PHB1 plays an important role in age-related diseases by affecting metabolic processes; however, the molecular mechanism behind aberrant PHB1 function is not known.