Uncoupling of Metabolic Health from Longevity through Genetic Alteration of Adipose Tissue Lipid-Binding Proteins

Cell Rep. 2017 Oct 10;21(2):393-402. doi: 10.1016/j.celrep.2017.09.051.


Deterioration of metabolic health is a hallmark of aging and generally assumed to be detrimental to longevity. Exposure to a high-calorie diet impairs metabolism and accelerates aging; conversely, calorie restriction (CR) prevents age-related metabolic diseases and extends lifespan. However, it is unclear whether preservation of metabolic health is sufficient to extend lifespan. We utilized a genetic mouse model lacking Fabp4/5 that confers protection against metabolic diseases and shares molecular and lipidomic features with CR to address this question. Fabp-deficient mice exhibit extended metabolic healthspan, with protection against insulin resistance and glucose intolerance, inflammation, deterioration of adipose tissue integrity, and fatty liver disease. Surprisingly, however, Fabp-deficient mice did not exhibit any extension of lifespan. These data indicate that extension of metabolic healthspan in the absence of CR can be uncoupled from lifespan, indicating the potential for independent drivers of these pathways, at least in laboratory mice.

Keywords: aging; calorie restriction; de novo lipogenesis; diabetes; fatty acid binding protein; inflammation; metabolic health; metaflammation; obesity.

MeSH terms

  • Adipose Tissue / growth & development
  • Adipose Tissue / metabolism*
  • Animals
  • Fatty Acid-Binding Proteins / genetics*
  • Fatty Acid-Binding Proteins / metabolism
  • Fatty Liver / genetics
  • Female
  • Insulin Resistance
  • Lipid Metabolism
  • Longevity*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism


  • Fabp4 protein, mouse
  • Fabp5 protein, mouse
  • Fatty Acid-Binding Proteins
  • Neoplasm Proteins