Female mice target deleted for the neuromedin B receptor have partial resistance to diet-induced obesity.
Previous studies have proposed a role for neuromedin B (NB), a bombesin-like peptide, in the control of body weight homeostasis. However, the nature of this role is unclear. The actions of NB are mediated preferentially by NB-preferring receptors (NBRs). Here we examined the consequences of targeted deletion of NBRs in female mice on body weight homeostasis in mice fed a normolipid diet (ND) or a high-fat diet (HFD) for 13 weeks. Body weight and food ingestion of neuromedin B receptor knockout (NBR-KO) mice fed a normolipid diet showed no difference in relation to wild-type (WT). However, the high-fat diet induced an 8.9- and 4.8-fold increase in body weight of WT and NBR-KO, respectively, compared to their controls maintained with a normolipid diet, even though the mice ingested the same amount of calories, regardless of genotype. Comparing mice fed the high-fat diet, NBR-KO mice accumulated approximately 45% less fat depot mass than WT, exhibited a lower percentage of fat in their carcasses (19.2 vs. 31.3%), and their adipocytes were less hypertrophied. Serum leptin and leptin mRNA in inguinal and perigonadal fat were lower in HFD NBR-KO than HFD WT, and serum adiponectin was similar among HFD groups and unaltered in comparison to ND-fed mice. HFD-fed WT mice developed glucose intolerance but not the HFD-fed NBR-KO mice, although they had similar glycaemia and insulinaemia. NBR-KO and WT mice on the normolipid diet showed no differences in any parameters, except for a trend to lower insulin levels. Therefore, disruption of the neuromedin B receptor pathway did not change body weight homeostasis in female mice fed a normolipid diet; however, it did result in partial resistance to diet-induced obesity.
Paula
Gabriela Silva Monteiro
GS
Laboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, bloco G, Ilha do Fundão, Rio de Janeiro, 21949-900, Brazil.
Souza
Luana Lopes
LL
Cabanelas
Adriana
A
Bloise
Flavia Fonseca
FF
Mello-Coelho
Valéria
V
Wada
Etsuko
E
Ortiga-Carvalho
Tania Maria
TM
Oliveira
Karen Jesus
KJ
Pazos-Moura
Carmen Cabanelas
CC
D052436:Adipose Tissue, White / Q000033:anatomy & histology; D000818:Animals; D001391:Azo Compounds; D001823:Body Composition / Q000235:genetics / Q000502:physiology; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D004396:Coloring Agents; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology; D002149:Energy Intake; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D005260:Female; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D006728:Hormones / Q000097:blood; D020738:Leptin / Q000096:biosynthesis / Q000235:genetics; D008055:Lipids / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics*; D018004:Receptors, Bombesin / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D001391:Azo Compounds; D004396:Coloring Agents; D004041:Dietary Fats; D006728:Hormones; D020738:Leptin; D008055:Lipids; D018004:Receptors, Bombesin; C011049:oil red O