| 1. |
- Cintron-Colon, Rigo, et al.
(författare)
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Activation of Kappa Opioid Receptor Regulates the Hypothermic Response to Calorie Restriction and Limits Body Weight Loss
- 2019
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 29:24, s. 4291-4299
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Tidskriftsartikel (refereegranskat)abstract
- Mammals maintain a nearly constant core body temperature (T-b) by balancing heat production and heat dissipation. This comes at a high metabolic cost that is sustainable if adequate calorie intake is maintained. When nutrients are scarce or experimentally reduced such as during calorie restriction (CR), endotherms can reduce energy expenditure by lowering T-b [1-6]. This adaptive response conserves energy, limiting the loss of body weight due to low calorie intake [710]. Here we show that this response is regulated by the kappa opioid receptor (KOR). CR is associated with increased hypothalamic levels of the endogenous opioid Leuenkephalin, which is derived from the KOR agonist precursor dynorphin [11]. Pharmacological inhibition of KOR, but not of the delta or the mu opioid receptor subtypes, fully blocked CR-induced hypothermia and increased weight loss during CR independent of calorie intake. Similar results were seen with DIO mice subjected to CR. In contrast, inhibiting KOR did not change T-b in animals fed ad libitum (AL). Chemogenetic inhibition of KOR neurons in the hypothalamic preoptic area reduced the CR-induced hypothermia, whereas chemogenetic activation of prodynorphin-expressing neurons in the arcuate or the parabrachial nucleus lowered T-b. These data indicate that KOR signaling is a pivotal regulator of energy homeostasis and can affect body weight during dieting by modulating T-b and energy expenditure.
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| 2. |
- Cintron-Colon, Rigo, et al.
(författare)
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Insulin-like growth factor 1 receptor regulates hypothermia during calorie restriction
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:36, s. 9731-9736
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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