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.
Highlights
Ames dwarf mice are diminutive, long-lived mutant mice
We hypothesize that the increased thermogenic demand and subsequent increased brown adipose tissue (BAT) activity may be partially responsible for the improved energy metabolism observed in Ames dwarf mice
Increased environmental temperature (eT) results in dwarf mice gaining weight without altering food consumption Increased eT lowers the need for thermogenesis, which in turn can lead to alterations in body weight
Summary
Ames dwarf mice are diminutive, long-lived mutant mice. Both their size and longevity stem from a recessive Prophet of Pituitary Factor 1 (Prop1) loss-of function mutation [1]. Our laboratory has demonstrated the relationship between decreased somatotropic (GH and IGF-1) signaling and improved energy metabolism in several studies [10,11,12,13] This relationship appears counterintuitive given i) GH is a highly lipolytic hormone, so its absence should theoretically lower the usage of lipids as metabolic fuel, ii) the severe hypopituitarism of dwarf mice should presumably lead to a slower rate of respiration, and iii) Ames dwarf mice have decreased levels of reactive oxygen species (ROS) [14,15,16], which given their increased metabolic rate, is opposite to the Rate of Living Hypothesis. We hypothesize that the increased thermogenic demand and subsequent increased BAT activity may be partially responsible for the improved energy metabolism observed in Ames dwarf mice
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