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2018 ; 115
(4
): 810-815
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Pyruvate induces torpor in obese mice
#MMPMID29311303
Soto M
; Orliaguet L
; Reyzer ML
; Manier ML
; Caprioli RM
; Kahn CR
Proc Natl Acad Sci U S A
2018[Jan]; 115
(4
): 810-815
PMID29311303
show ga
Mice subjected to cold or caloric deprivation can reduce body temperature and
metabolic rate and enter a state of torpor. Here we show that administration of
pyruvate, an energy-rich metabolic intermediate, can induce torpor in mice with
diet-induced or genetic obesity. This is associated with marked hypothermia,
decreased activity, and decreased metabolic rate. The drop in body temperature
correlates with the degree of obesity and is blunted by housing mice at
thermoneutrality. Induction of torpor by pyruvate in obese mice relies on
adenosine signaling and is accompanied by changes in brain levels of hexose
bisphosphate and GABA as detected by mass spectroscopy-based imaging. Pyruvate
does not induce torpor in lean mice but results in the activation of brown
adipose tissue (BAT) with an increase in the level of uncoupling protein-1
(UCP1). Denervation of BAT in lean mice blocks this increase in UCP1 and allows
the pyruvate-induced torpor phenotype. Thus, pyruvate administration induces
torpor in obese mice by pathways involving adenosine and GABA signaling and a
failure of normal activation of BAT.
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