Activation of Kappa Opioid Receptor Regulates the Hypothermic Response to Calorie Restriction and Limits Body Weight Loss.
Level 5 - mechanism / opinion, no new human data
Animal and mechanistic laboratory study without human clinical data
PubMed 31786059 · doi:10.1016/j.cub.2019.10.027
What was done
Researchers investigated the role of kappa opioid receptor (KOR) signaling in regulating core body temperature and weight loss during calorie restriction (CR) in lean and diet-induced obese (DIO) mice. They evaluated hypothalamic Leu-enkephalin levels, tested pharmacological blockade of KOR, delta, and mu opioid receptors in CR and ad libitum-fed mice, and used chemogenetics to inhibit preoptic KOR neurons or activate prodynorphin-expressing neurons in the arcuate and parabrachial nuclei.
What was found
The abstract reports no numerical values, effect sizes, or exact temperature changes. Calorie restriction increased hypothalamic Leu-enkephalin levels. Pharmacological inhibition of KOR, but not delta or mu opioid receptors, fully blocked CR-induced hypothermia and increased weight loss during CR in both lean and DIO mice without changing caloric intake. KOR inhibition did not alter core body temperature in mice fed ad libitum. Chemogenetic inhibition of preoptic KOR neurons reduced CR-induced hypothermia, while activation of prodynorphin neurons in the arcuate or parabrachial nucleus decreased core body temperature.
Why it matters
This study identifies central KOR signaling as a critical regulator of adaptive hypothermia and energy conservation during food scarcity. Understanding this pathway may inform interventions aimed at overcoming metabolic adaptation during weight loss.
Limits
The study was conducted exclusively in rodent models, so direct applicability to human energy homeostasis is unknown. The abstract does not provide sample sizes, quantitative measurements of body temperature or weight change, or variance estimates.
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- supports Dynorphin is part of the thermoregulatory pathway and acts to cool the body down when body temperature rises.