Increased environmental temperature normalizes energy metabolism outputs between normal and Ames dwarf mice

Aging (Albany NY). 2018 Oct 18;10(10):2709-2722. doi: 10.18632/aging.101582.

Abstract

Ames dwarf (Prop1df) mice possess a loss-of-function mutation that results in deficiency of growth hormone, prolactin, and thyroid-stimulating hormone, as well as exceptional longevity. Work in other laboratories suggests that increased respiration and lipid utilization are important for maximizing mammalian longevity. Interestingly, these phenotypes are observed in Ames dwarf mice. We recently demonstrated that Ames dwarf mice have hyperactive brown adipose tissue (BAT), and hypothesized that this may in part be due to their increased surface to mass ratio leading to increased heat loss and an increased demand for thermogenesis. Here, we used increased environmental temperature (eT) to interrogate this hypothesis. We found that increased eT diminished BAT activity in Ames dwarf mice, and led to the normalization of both VO2 and respiratory quotient between dwarf and normal mice, as well as partial normalization (i.e. impairment) of glucose homeostasis in Ames dwarf mice housed at an increased eT. Together, these data suggest that an increased demand for thermogenesis is partially responsible for the improved energy metabolism and glucose homeostasis which are observed in Ames dwarf mice.

Keywords: Ames dwarf; aging; energy metabolism; thermogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, Brown / physiopathology
  • Adiposity
  • Animals
  • Dwarfism / genetics
  • Dwarfism / metabolism*
  • Dwarfism / physiopathology
  • Energy Metabolism* / genetics
  • Environment, Controlled*
  • Genetic Predisposition to Disease
  • Glucose / metabolism*
  • Heating*
  • Homeodomain Proteins / genetics
  • Homeostasis
  • Loss of Function Mutation
  • Male
  • Mice, Mutant Strains
  • Phenotype
  • Thermogenesis

Substances

  • Homeodomain Proteins
  • Prophet of Pit-1 protein
  • Glucose