Insulin-like growth factor 1 receptor regulates hypothermia during calorie restriction

When food resources are scarce, endothermic animals can lower core body temperature (Tb). This phenomenon is believed to be part of an adaptive mechanism that may have evolved to conserve energy until more food becomes available. Here, we found in the mouse that the insulin-like growth factor 1 receptor (IGF-1R) controls this response in the central nervous system. Pharmacological or genetic inhibition of IGF-1R enhanced the reduction of temperature and of energy expenditure during calorie restriction. Full blockade of IGF-1R affected female and male mice similarly. In contrast, genetic IGF-1R dosage was effective only in females, where it also induced transient and estrusspecific hypothermia in animals fed ad libitum. These effects were regulated in the brain, as only central, not peripheral, pharmacological activation of IGF-1R prevented hypothermia during calorie restriction. Targeted IGF-1R knockout selectively in forebrain neurons revealed that IGF signaling also modulates calorie restriction-dependent Tb regulation in regions rostral of the canonical hypothalamic nuclei involved in controlling body temperature. In aggregate, these data identify central IGF-1R as a mediator of the integration of nutrient and temperature homeostasis. They also show that calorie restriction, IGF-1R signaling, and body temperature, three of the main regulators of metabolism, aging, and longevity, are components of the same pathway.

Sanchez-Alavez, Manuel (författare)
Nguyen, William (författare)
Mori, Simone (författare)
Gonzalez-Rivera, Ruben (författare)
Lien, Tiffany (författare)
Bartfai, TamasStockholms universitet,Institutionen för neurokemi(Swepub:su)tbart (författare)
Aid, Saba (författare)
Francois, Jean-Christophe (författare)
Holzenbergerf, Martin (författare)
Conti, Bruno (författare)
Stockholms universitetInstitutionen för neurokemi (creator_code:org_t)

Ingår i:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences114:36, s. 9731-97360027-84241091-6490

Av författaren/redakt...: Cintron-Colon, R ...; Sanchez-Alavez, ...; Nguyen, William; Mori, Simone; Gonzalez-Rivera, ...; Lien, Tiffany; visa fler...; Bartfai, Tamas; Aid, Saba; Francois, Jean-C ...; Holzenbergerf, M ...; Conti, Bruno; visa färre...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Neurovetenskaper

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.