title: Mice lacking δ-opioid receptors resist the development of diet-induced obesity.
abstract: Pharmacological manipulation of opioid receptors alters feeding behavior. However, the individual contributions of each opioid receptor subtype on energy balance remain largely unknown. Herein, we investigated whether genetic disruption of the δ-opioid receptor (DOR) also controls energy homeostasis. Mice lacking DOR and wild-type mice were fed with standard diet and high-energy diet (HED). Mice were analyzed in vivo with the indirect calorimetry system, and tissues were analyzed by real-time PCR and Western blot analysis. DOR-knockout (KO) mice gained less weight (P<0.01) and had lower fat mass (P<0.01) when compared to WT mice fed an HED. Although DOR-KO mice were hyperphagic, they showed higher energy expenditure (P<0.05), which was the result of an increased activation of the thermogenic program in brown adipose tissue. The increased nonshivering thermogenesis involved the stimulation of uncoupling protein 1 (UCP1; P<0.01), peroxisome proliferator-activated receptor γ coactivator (PGC1α; P<0.05), and fibroblast growth factor 21 (FGF21; P<0.01). DOR deficiency also led to an attenuation of triglyceride content in the liver (P<0.05) in response to an HED. These findings reveal a novel role of DOR in the control of thermogenic markers and energy expenditure, and they provide a potential new therapeutic approach for the treatment of obesity.
authors.affiliation: Obesity Research, Lilly Research Laboratories, Indianapolis, Indiana, USA.
authors.forename: Traci A
authors.initials: TA
authors.lastname: Czyzyk
authors.forename: Amparo
authors.initials: A
authors.lastname: Romero-Picó
authors.forename: John
authors.initials: J
authors.lastname: Pintar
authors.forename: Jaime H
authors.initials: JH
authors.lastname: McKinzie
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Tschöp
authors.forename: Michael A
authors.initials: MA
authors.lastname: Statnick
authors.forename: Ruben
authors.initials: R
authors.lastname: Nogueiras
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology*; D017465:Receptors, Opioid, delta / Q000172:deficiency*; D022722:Thermogenesis / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism
chemical_list: D017465:Receptors, Opioid, delta; D014280:Triglycerides; D005947:Glucose