Pyruvate induces torpor in obese mice.

Soto M, Orliaguet L, Reyzer ML, Manier ML, Caprioli RM, Kahn CR
Proc Natl Acad Sci U S A. 2018 115 (4): 810-815

PMID: 29311303 · PMCID: PMC5789941 · DOI:10.1073/pnas.1717507115

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.

MeSH Terms (12)

Adenosine Adipose Tissue, Brown Animals Brain Insulin Resistance Male Mice, Inbred C57BL Mice, Obese Obesity Pyruvic Acid Torpor Uncoupling Protein 1

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